Articoli di riviste: "Antitumoral properties"

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Fabiani, Roberto. "Antitumoral Properties of Natural Products". Molecules 25, n. 3 (3 febbraio 2020): 650. http://dx.doi.org/10.3390/molecules25030650.

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McLachlan, J. A., C. D. Serkin, K. M. Morrey e O. Bakouche. "Antitumoral properties of aged human monocytes." Journal of Immunology 154, n. 2 (15 gennaio 1995): 832–43. http://dx.doi.org/10.4049/jimmunol.154.2.832.

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Abstract It is known that older people are more sensitive to cancer and infectious agents and need more time to recover from such disorders. Can this difference in sensitivity to cancer and infections between elderly and younger people be a result of a difference in their immune systems and, more specifically, in the way monocytes react to infectious agents and cancer cells? To determine what happens after cells have aged, human monocytes were purified from young donors (approximately 25 years of age) and from older donors (65 years of age or older) and tested for their ability to respond to the polyclonal activator LPS. Our results showed that monocytes from aged donors (aged monocytes), when compared with monocytes from younger donors (young monocytes) did lose part of their cytotoxicity against tumor cells (A375 human melanoma cells and L929 murine fibroblast cells). In addition, aged monocytes displayed a sharp decrease in IL-1 secretion, but did display the intracellular 31 kDa IL-1 precursor. Moreover, aged monocytes displayed a decrease in the production of reactive oxygen intermediates such as NO2 and H2O2. Finally, aged monocytes stimulated by LPS displayed an increase in intracellular cyclic AMP and have lost their protein kinase C translocation from the cytosol to the plasma membranes. These results suggest that age affects the immunologic and antitumoral properties of human monocytes.

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Braca, A. "Insight on antitumoral properties of plant diterpenes". Planta Medica 81, S 01 (14 dicembre 2016): S1—S381. http://dx.doi.org/10.1055/s-0036-1596105.

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Pandiella-Alonso, Atanasio, Elena Díaz-Rodríguez e Eduardo Sanz. "Antitumoral Properties of the Nutritional Supplement Ocoxin Oral Solution: A Comprehensive Review". Nutrients 12, n. 9 (31 agosto 2020): 2661. http://dx.doi.org/10.3390/nu12092661.

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Ocoxin Oral Solution (OOS) is a nutritional supplement whose formulation includes several plant extracts and natural products with demonstrated antitumoral properties. This review summarizes the antitumoral action of the different constituents of OOS. The action of this formulation on different preclinical models as well as clinical trials is reviewed, paying special attention to the mechanism of action and quality of life improvement properties of this nutritional supplement. Molecularly, its mode of action includes a double edge role on tumor biology, that involves a slowdown in cell proliferation accompanied by cell death induction. Given the safety and good tolerability of OOS, and its potentiation of the antitumoral effect of other standard of care drugs, OOS may be used in the oncology clinic in combination with conventional therapies.

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Lungu, Claudiu N., Bogdan Ionel Bratanovici, Maria Mirabela Grigore, Vasilichia Antoci e Ionel I. Mangalagiu. "Hybrid Imidazole-Pyridine Derivatives: An Approach to Novel Anticancer DNA Intercalators". Current Medicinal Chemistry 27, n. 1 (18 febbraio 2020): 154–69. http://dx.doi.org/10.2174/0929867326666181220094229.

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Lack of specificity and subsequent therapeutic effectiveness of antimicrobial and antitumoral drugs is a common difficulty in therapy. The aim of this study is to investigate, both by experimental and computational methods, the antitumoral and antimicrobial properties of a series of synthesized imidazole-pyridine derivatives. Interaction with three targets was discussed: Dickerson-Drew dodecamer (PDB id 2ADU), G-quadruplex DNA string (PDB id 2F8U) and DNA strain in complex with dioxygenase (PDB id 3S5A). Docking energies were computed and represented graphically. On them, a QSAR model was developed in order to further investigate the structure-activity relationship. Results showed that synthesized compounds have antitumoral and antimicrobial properties. Computational results agreed with the experimental data.

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Iacopetta, Domenico, Jessica Ceramella, Alessia Catalano, Carmela Saturnino, Maria Grazia Bonomo, Carlo Franchini e Maria Stefania Sinicropi. "Schiff Bases: Interesting Scaffolds with Promising Antitumoral Properties". Applied Sciences 11, n. 4 (20 febbraio 2021): 1877. http://dx.doi.org/10.3390/app11041877.

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Schiff bases, named after Hugo Schiff, are highly reactive organic compounds broadly used as pigments and dyes, catalysts, intermediates in organic synthesis, and polymer stabilizers. Lots of Schiff bases are described in the literature for various biological activities, including antimalarial, antibacterial, antifungal, anti-inflammatory, and antiviral. Schiff bases are also known for their ability to form complexes with several metals. Very often, complexes of Schiff bases with metals and Schiff bases alone have demonstrated interesting antitumor activity. Given the innumerable vastness of data regarding antitumor activity of all these compounds, we focused our attention on mono- and bis-Schiff bases alone as antitumor agents. We will highlight the most significant examples of compounds belonging to this class reported in the literature.

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Perez-Tomas, R., e M. Vinas. "New Insights on the Antitumoral Properties of Prodiginines". Current Medicinal Chemistry 17, n. 21 (1 luglio 2010): 2222–31. http://dx.doi.org/10.2174/092986710791331103.

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Nava-Villalba, Mario, e Carmen Aceves. "6-Iodolactone, key mediator of antitumoral properties of iodine". Prostaglandins & Other Lipid Mediators 112 (agosto 2014): 27–33. http://dx.doi.org/10.1016/j.prostaglandins.2014.07.001.

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Adam, Gigi, Florina Daniela Cojocaru, Liliana Verestiuc, Oana Cioanca, Ingrid-Andrada Vasilache, Ana-Maria Adam, Cornelia Mircea et al. "Assessing the Antioxidant Properties, In Vitro Cytotoxicity and Antitumoral Effects of Polyphenol-Rich Perilla leaves Extracts". Antioxidants 13, n. 1 (29 dicembre 2023): 58. http://dx.doi.org/10.3390/antiox13010058.

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(1) Background: This study aimed to outline the antioxidant, antitumoral, and cytotoxic proprieties of various types of Perilla frutescens extracts obtained from the leaves of the species. (2) Methods: We determined total polyphenols, flavonoids and anthocyanins contents, as well as the in vitro antioxidant, antitumoral, and cytotoxic actions in three types of ethanolic extracts (E1, E2, E3) and in three types of acetone: ethanol extracts (A1, A2, A3) of Perilla frutescens according to standardized procedures. (3) Results: We found that Perilla frutescens ethanolic extracts had the highest total phenol and anthocyanins concentrations. The flavonoids concentration was not statistically different between the extracts. The iron chelating capacity, hydroxyl radical scavenging capacity, superoxide anion radical scavenging capacity, and lipoxygenase inhibition capacity showed a significant increase with higher concentrations of Perilla frutescens extracts, particularly the ethanolic extracts. Perillyl alcohol had greater cytotoxic capacity in the MG-63 cell line and E1 extract showed similar significant cytotoxic effects in the A431 cell line. (4) Conclusions: Both ethanolic and acetone–ethanol extracts from Perilla frutescens exhibited important antioxidant and antitumoral actions in vitro, which proportionally increased with concentration. The cytotoxic threshold determined in this study for various types of extracts could help determine the best dosage with the maximum antioxidant and antitumoral potential. Our results could serve as a basis for further studies that will investigate the cytotoxic effects of Perilla frutescens variants on various types of cancer cell lines.

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Esteruelas, Gerard, Eliana B. Souto, Marta Espina, María Luisa García, Marta Świtalska, Joanna Wietrzyk, Anna Gliszczyńska e Elena Sánchez-López. "Diclofenac Loaded Biodegradable Nanoparticles as Antitumoral and Antiangiogenic Therapy". Pharmaceutics 15, n. 1 (28 dicembre 2022): 102. http://dx.doi.org/10.3390/pharmaceutics15010102.

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Cancer is identified as one of the main causes of death worldwide, and an effective treatment that can reduce/eliminate serious adverse effects is still an unmet medical need. Diclofenac, a non-steroidal anti-inflammatory drug (NSAID), has demonstrated promising antitumoral properties. However, the prolonged use of this NSAID poses several adverse effects. These can be overcome by the use of suitable delivery systems that are able to provide a controlled delivery of the payload. In this study, Diclofenac was incorporated into biodegradable polymeric nanoparticles based on PLGA and the formulation was optimized using a factorial design approach. A monodisperse nanoparticle population was obtained with a mean size of ca. 150 nm and negative surface charge. The release profile of diclofenac from the optimal formulation followed a prolonged release kinetics. Diclofenac nanoparticles demonstrated antitumoral and antiangiogenic properties without causing cytotoxicity to non-tumoral cells, and can be pointed out as a safe, promising and innovative nanoparticle-based formulation with potential antitumoral effects.

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Klaiss-Luna, Maria C., Juan M. Giraldo-Lorza, Małgorzata Jemioła-Rzemińska, Kazimierz Strzałka e Marcela Manrique-Moreno. "Biophysical Insights into the Antitumoral Activity of Crotalicidin against Breast Cancer Model Membranes". International Journal of Molecular Sciences 24, n. 22 (12 novembre 2023): 16226. http://dx.doi.org/10.3390/ijms242216226.

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Bioactive peptides have emerged as promising therapeutic agents with antimicrobial, antifungal, antiparasitic, and, recently, antitumoral properties with a mechanism of action based on membrane destabilization and cell death, often involving a conformational change in the peptide. This biophysical study aims to provide preliminary insights into the membrane-level antitumoral mode of action of crotalicidin, a cationic host defense peptide from rattlesnake venom, toward breast cancer cell lines. The lipid composition of breast cancer cell lines was obtained after lipid extraction and quantification to prepare representative cell membrane models. Membrane–peptide interaction studies were performed using differential scanning calorimetry and Fourier-transform infrared spectroscopy. The outcome evidences the potential antitumoral activity and selectivity of crotalicidin toward breast cancer cell lines and suggests a mechanism initiated by the electrostatic interaction of the peptide with the lipid bilayer surface and posterior conformation change with membrane intercalation between the acyl chains in negatively charged lipid systems. This research provides valuable information that clears up the antitumoral mode of action of crotalicidin.

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Sánchez-Quesada, Cristina, Francisco Gutiérrez-Santiago, Carmen Rodríguez-García e José J. Gaforio. "Synergistic Effect of Squalene and Hydroxytyrosol on Highly Invasive MDA-MB-231 Breast Cancer Cells". Nutrients 14, n. 2 (7 gennaio 2022): 255. http://dx.doi.org/10.3390/nu14020255.

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Several studies relate Mediterranean diet and virgin olive oil (VOO) intake with lower risk of several chronic diseases, including breast cancer. Many of them described antitumor properties of isolated minor compounds present in VOO, but beneficial properties of VOO arise from the effects of all its compounds acting together. The aim of the present study was to test the antitumor effects of two minor compounds from VOO (hydroxytyrosol (HT) and squalene (SQ)) on highly metastatic human breast tumor cells (MDA-MB-231) when acting in combination. Both isolated compounds were previously analyzed without showing any antitumoral effect on highly invasive MDA-MB-231 breast cancer cells, but the present results show that HT at 100 µM, combined with different concentrations of SQ, could exert antitumor effects. When they are combined, HT and SQ are able to inhibit cell proliferation, promoting apoptosis and DNA damage in metastatic breast cancer cells. Therefore, our results suggest that the health-promoting properties of VOO may be due, at least in part, to the combined action of these two minor compounds.

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Kozlova, A. I., E. V. Voropayev e A. I. Konoplya. "THE ROLE OF DENDRITIC CELLS IN FORMATION OF ANTITUMORAL IMMUNITY (literature review)". Health and Ecology Issues, n. 4 (28 dicembre 2014): 19–24. http://dx.doi.org/10.51523/2708-6011.2014-11-4-3.

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At present, dendritic cells are thought to be the main «professional» antigenpresenting cells. They play the leading role in the triggering of the adaptive immune response and its integration with inborn immunity. These properties of dendritic cells determine significant interest for their possible use as a base for making antitumoral vaccines. The results of the study testify about the amplification of the lymphocytes antitumoral activity in relation to the types of tumors against which DC-vaccination was carried out.

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Diez, Marta Martínez, María José Muñoz-Alonso, Gema Santamaría Nuñez, María José Guillén, María Ángela Oliva, Eva Maria Garrido-Martin, Pablo Avilés, J. Fernando Díaz e Carmen Cuevas. "Abstract 6243: The novel antitubulin agent PM534 exhibits potent antitumoral and antiangiogenic properties in vitro and in vivo". Cancer Research 83, n. 7_Supplement (4 aprile 2023): 6243. http://dx.doi.org/10.1158/1538-7445.am2023-6243.

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Abstract Background: Microtubule targeting agents have demonstrated to be very effective antitumoral drugs. The development of novel anti-tubulin agents with more efficient mechanisms of action presents several challenges due to their poor solubility, troublesome synthesis or purification, and toxicities. In this work, we present the novel anti-tubulin agent PM534, a synthetic small molecule that shows efficient antitumoral and antiangiogenic properties in vitro and in vivo. Methods and Results: PM534 exhibits a potent antitumor activity in vitro with a mean GI50 value in the low nanomolar range in several different human cancer cell lines. Washout in vitro experiments show irreversible cellular effects after 1h in contact with the compound, compelling the cells to apoptotic cell death likely due to PM534 induced disorganization of the tubulin cytoskeleton. PM534 inhibits migration and invasion of tumor cells in vitro, and arrests the cell cycle in the G2/M phase, forcing them to apoptosis. In addition, PM534 presents potent antiangiogenic effects in vitro, robustly inhibiting endothelial cells proliferation and migration, and the formation of angiotubes. The in vivo antitumor activity of PM534 was characterized in human-derived tumors xenografted in athymic nu/nu mice, namely breast (MDA-MB-231), and pancreas (Mia-Paca-2). PM534 was intravenously administered once per week for three consecutive weeks at 5.0 mg/kg. In vivo PM534-induced antitumor activity (vs. placebo) was seen in MDA-MB-231 (T/C, 0.3% on Day 28; TV, p<0.0001) and Mia-Paca-2 (21.3% on Day 21; TV, p<0.0001). Also, PM534 treatment increased with statistical significance (vs. placebo) the median survival time of mice bearing MDA-MB-231 (82 vs. 33 days; p<0.0001) and Mia-Paca-2 (51 vs. 30 days; p=0.0008). Of note, complete tumor remissions were observed in 2/10 (lasting 11 days and 161 days, each), and 10/10 (lasting 45 days in 9/10 and 140 days in 1/10) PM534-treated animals bearing Mia-Paca-2 and MDA-MB-231 and tumors, respectively. Conclusions: Based on in vitro activity against different human tumor cell lines, in vivo activity in xenografted human tumors, as well as on its anti-angiogenic properties, the safety, pharmacology and preliminary antitumor activity of PM534 will be evaluated in a first-in-human clinical trial to be conducted in patients with advanced solid tumors. Citation Format: Marta Martínez Diez, María José Muñoz-Alonso, Gema Santamaría Nuñez, María José Guillén, María Ángela Oliva, Eva Maria Garrido-Martin, Pablo Avilés, J. Fernando Díaz, Carmen Cuevas. The novel antitubulin agent PM534 exhibits potent antitumoral and antiangiogenic properties in vitro and in vivo. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6243.

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Wang, Xiaohong, Jianxin Li, Jianghua He e Jingfu Liu. "Synthesis, Properties and Biological Activity of Organotitanium Substituted Heteropolytungstates". Metal-Based Drugs 8, n. 4 (1 gennaio 2001): 179–82. http://dx.doi.org/10.1155/mbd.2001.179.

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Six new compounds [(CpTi)XW11O39]n− (Cp=η5-C5H5, X=Ge, Ga, B) have been prepared and their Keggin structures determined by elementary analysis, IR, UV, H1 NMR and W183 NMR spectrometry. The results show that the complexes retain Keggin structure. The complexes exhibit antitumoral activity in vitro as shown by MTT experiment.

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Mašković, Jelena M., Antonios Hatzidimitriou, Ana Damjanović, Tatjana P. Stanojković, Srećko R. Trifunović, Athina A. Geronikaki e Dionysia Papagiannopoulou. "Synthesis, characterization and biological evaluation of Pd(ii), Cu(ii), Re(i) and 99mTc(i) thiazole-based complexes". MedChemComm 9, n. 5 (2018): 831–42. http://dx.doi.org/10.1039/c8md00067k.

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Măciucă, Ana-Mădălina, Mihaela Badea, Rodica Olar, Alexandra Cristina Munteanu e Valentina Uivarosi. "Synthesis and Physico-Chemical Characterization of the Cu(II), Pd(II) and Ru(III) Complexes with Difloxacin". Proceedings 29, n. 1 (15 ottobre 2019): 65. http://dx.doi.org/10.3390/proceedings2019029065.

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The growing interest in metal-quinolone complexes is sustained by a large number of compounds obtained and tested for antibacterial [1], antitumoral [1,2], antifungal [1], and antiparasitic [3] properties. [...]

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Sanchez-Martin, Victoria, María del Carmen Plaza-Calonge, Ana Soriano-Lerma, Matilde Ortiz-Gonzalez, Angel Linde-Rodriguez, Virginia Perez-Carrasco, Inmaculada Ramirez-Macias et al. "Gallic Acid: A Natural Phenolic Compound Exerting Antitumoral Activities in Colorectal Cancer via Interaction with G-Quadruplexes". Cancers 14, n. 11 (26 maggio 2022): 2648. http://dx.doi.org/10.3390/cancers14112648.

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Natural phenolic compounds have gained momentum for the prevention and treatment of cancer, but their antitumoral mechanism of action is not yet well understood. In the present study, we screened the antitumoral potential of several phenolic compounds in a cellular model of colorectal cancer (CRC). We selected gallic acid (GA) as a candidate in terms of potency and selectivity and extensively evaluated its biological activity. We report on the role of GA as a ligand of DNA G-quadruplexes (G4s), explaining several of its antitumoral effects, including the transcriptional inhibition of ribosomal and CMYC genes. In addition, GA shared with other established G4 ligands some effects such as cell cycle arrest, nucleolar stress, and induction of DNA damage. We further confirmed the antitumoral and G4-stabilizing properties of GA using a xenograft model of CRC. Finally, we succinctly demonstrate that GA could be explored as a therapeutic agent in a patient cohort with CRC. Our work reveals that GA, a natural bioactive compound present in the diet, affects gene expression by interaction with G4s both in vitro and in vivo and paves the way towards G4s targeting with phenolic compounds.

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Kalechman, Y., A. Shani, S. Dovrat, J. K. Whisnant, K. Mettinger, M. Albeck e B. Sredni. "The antitumoral effect of the immunomodulator AS101 and paclitaxel (Taxol) in a murine model of lung adenocarcinoma." Journal of Immunology 156, n. 3 (1 febbraio 1996): 1101–9. http://dx.doi.org/10.4049/jimmunol.156.3.1101.

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Abstract The immunomodulator ammonium trichloro(dioxyethylene-0-0')tellurate (AS101) has been shown to possess antitumoral properties in several murine models. In the present study, we demonstrate a synergistic in vivo antitumor effect of AS101 and Taxol against early stage Madison 109 lung adenocarcinoma. Treatment with optimal doses of Taxol (25 and 17 mg/kg) and AS101 (0.5 mg/kg) resulted in 66.6 and 43.3% cures. We propose that the antitumor effect is the result of both a direct and indirect effect of the drugs on tumor cells. AS101 and Taxol directly inhibited clonogenicity of M109 cells in a synergistic dose-dependent manner. Exposure of M109 cells to clinically achievable concentrations of Taxol and AS101 produced a synergistic internucleosomal DNA fragmentation associated with programmed cell death. We suggest that AS101 renders tumor cells more susceptible to chemotherapy in general and to Taxol in particular, partly by increasing the wild-type p53 protein expression that is required for efficient execution of the death program. Moreover, we demonstrate a synergistic effect of AS101 and Taxol in increasing the tumoricidal activity of macrophages. This activity is produced by nitric oxide secretion. The synergistic antitumoral effects of AS101 and Taxol were partly ablated both in vitro and in vivo by inhibition of nitric oxide synthase. These findings indicate that AS101 in combination with Taxol may be a promising antitumor drug, and illustrate the mechanism of action of both drugs when acting synergistically. Phase II clinical trials have been initiated using AS101 in combination with Taxol.

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Cudalbeanu, Mihaela, Bianca Furdui, Geta Cârâc, Vasilica Barbu, Alina Viorica Iancu, Fernanda Marques, Jorge Humberto Leitão, Sílvia Andreia Sousa e Rodica Mihaela Dinica. "Antifungal, Antitumoral and Antioxidant Potential of the Danube Delta Nymphaea alba Extracts". Antibiotics 9, n. 1 (21 dicembre 2019): 7. http://dx.doi.org/10.3390/antibiotics9010007.

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This study aimed to explore for the first time the biological properties such as antifungal, antitumoral and antioxidant of Danube Delta Nymphaea alba (N. alba) leaf and root methanolic extracts. The toxicity studies of N. alba extracts showed no inhibitory effect on wheat seed germination by evaluating the most sensitive physiological parameters (Germination %, Germination index, Vigor index) and using confocal laser scanning microscopy images. The analyzed extracts were found to have high antifungal activity against Candida glabrata with MIC values of 1.717 µg/mL for leaf and 1.935 µg/mL for root. The antitumor activity of the both extracts against A2780/A2780cisR ovarian, LNCaP prostate and MCF-7 breast cancer cells was promising with IC50 values ranging from 23–274 µg/mL for leaf and 18–152 µg/mL for root, and the combination of N. alba extracts with cisplatin showed a synergistic effect (coefficient of drug interaction <1). The antioxidant properties were assessed by β-carotene bleaching, ABTS and FRAP assays and cyclic voltammetry. Quercetin, the most prominent antioxidant, was quantified in very good yields by spectroelectrochemical assay.

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Pérez-Peña, Javier, Elena Díaz-Rodríguez, Eduardo Sanz e Atanasio Pandiella. "Central Role of Cell Cycle Regulation in the Antitumoral Action of Ocoxin". Nutrients 11, n. 5 (14 maggio 2019): 1068. http://dx.doi.org/10.3390/nu11051068.

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Nutritional supplements which include natural antitumoral compounds could represent safe and efficient additives for cancer patients. One such nutritional supplement, Ocoxin Oral solution (OOS), is a composite formulation that contains several antioxidants and exhibits antitumoral properties in several in vitro and in vivo tumor conditions. Here, we performed a functional genomic analysis to uncover the mechanism of the antitumoral action of OOS. Using in vivo models of acute myelogenous leukemia (AML, HEL cells, representative of a liquid tumor) and small-cell lung cancer (GLC-8, representative of a solid tumor), we showed that OOS treatment altered the transcriptome of xenografted tumors created by subcutaneously implanting these cells. Functional transcriptomic studies pointed to a cell cycle deregulation after OOS treatment. The main pathway responsible for this deregulation was the E2F–TFDP route, which was affected at different points. The alterations ultimately led to a decrease in pathway activation. Moreover, when OOS-deregulated genes in the AML context were analyzed in patient samples, a clear correlation with their levels and prognosis was observed. Together, these data led us to suggest that the antitumoral effect of OOS is due to blockade of cell cycle progression mainly caused by the action of OOS on the E2F–TFDP pathway.

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Azar, Fadi, Jules Deforges, Christelle Demeusoit, Patricia Kleinpeter, Christelle Remy, Nathalie Silvestre, Johann Foloppe et al. "TG6050, an oncolytic vaccinia virus encoding interleukin-12 and anti-CTLA-4 antibody, favors tumor regression via profound immune remodeling of the tumor microenvironment". Journal for ImmunoTherapy of Cancer 12, n. 7 (luglio 2024): e009302. http://dx.doi.org/10.1136/jitc-2024-009302.

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BackgroundTG6050 was designed as an improved oncolytic vector, combining the intrinsic properties of vaccinia virus to selectively replicate in tumors with the tumor-restricted expression of recombinant immune effectors to modify the tumor immune phenotype. These properties might be of particular interest for “cold” tumors, either poorly infiltrated or infiltrated with anergic T cells.Methods TG6050, an oncolytic vaccinia virus encodes single-chain human interleukin-12 (hIL-12) and full-length anti-cytotoxic T-lymphocyte-associated antigen-4 (@CTLA-4) monoclonal antibody. The relevant properties of TG6050 (replication, cytopathy, transgenes expression and functionality) were extensively characterizedin vitro. The biodistribution and pharmacokinetics of the viral vector, @CTLA-4 and IL-12, as well as antitumoral activities (alone or combined with immune checkpoint inhibitors) were investigated in several “hot” (highly infiltrated) and “cold” (poorly infiltrated) syngeneic murine tumor models. The mechanism of action was deciphered by monitoring both systemic and intratumoral immune responses, and by tumor transcriptome analysis. The safety of TG6050 after repeated intravenous administrations was evaluated in cynomolgus monkeys, with a focus on the level of circulating IL-12.ResultsMultiplication and propagation of TG6050 in tumor cellsin vitroandin vivowere associated with local expression of functional IL-12 and @CTLA-4. This dual mechanism translated into a strong antitumoral activity in both “cold” and “hot” tumor models (B16F10, LLC1 or EMT6, CT26, respectively) that was further amplified when combined with anti-programmed cell death protein-1. Analysis of changes in the tumor microenvironment (TME) after treatment with TG6050 showed increases in interferon-gamma, of CD8+T cells, and of M1/M2 macrophages ratio, as well as a drastic decrease of regulatory T cells. These local modifications were observed alongside bolstering a systemic and specific antitumor adaptive immune response. In toxicology studies, TG6050 did not display any observable adverse effects in cynomolgus monkeys.ConclusionsTG6050 effectively delivers functional IL-12 and @CTLA-4 into the tumor, resulting in strong antitumor activity. The shift towards an inflamed TME correlated with a boost in systemic antitumor T cells. The solid preclinical data and favorable benefit/risk ratio paved the way for the clinical evaluation of TG6050 in metastatic non-small cell lung cancer (NCT05788926trial in progress).

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Sin, Zi Wayne, Vipul Bhardwaj, Amit Kumar Pandey e Manoj Garg. "A brief overview of antitumoral actions of bruceine D". Exploration of Targeted Anti-tumor Therapy 1, n. 4 (21 luglio 2020): 200–217. http://dx.doi.org/10.37349/etat.2020.00013.

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Cancer remains the second leading cause of mortality globally. In combating cancer, conventional chemotherapy and/or radiotherapy are administered as first-line therapy. However, these are usually accompanied with adverse side effects that decrease the quality of patient’s lives. As such, natural bioactive compounds have gained an attraction in the scientific and medical community as evidence of their anticancer properties and attenuation of side effects mounted. In particular, quassinoids have been found to exhibit a plethora of inhibitory activities such as anti-proliferative effects on tumor development and metastasis. Recently, bruceine D, a quassinoid isolated from the shrub Brucea javanica (L.) Merr. (Simaroubaceae), has come under immense investigation on its antineoplastic properties in various human cancers including pancreas, breast, lung, blood, bone, and liver. In this review, we have highlighted the antineoplastic effects of bruceine D and its mode of actions in different tumor models.

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Pérez-Larrán, Patricia, Elena M. Balboa, María Dolores Torres e Herminia Domínguez. "Antioxidant and Antitumoral Properties of Aqueous Fractions from Frozen Sargassum muticum". Waste and Biomass Valorization 11, n. 4 (18 settembre 2018): 1261–69. http://dx.doi.org/10.1007/s12649-018-0456-x.

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Williams, Patricia A. M., Juan Zinczuk, Daniel A. Barrio, Oscar E. Piro, Otaciro R. Nascimento e Susana B. Etcheverry. "Potential antitumoral properties of a new copper complex with santonic acid". Bioorganic & Medicinal Chemistry 16, n. 8 (aprile 2008): 4313–22. http://dx.doi.org/10.1016/j.bmc.2008.02.075.

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Bento, Ananda de Araujo, Marianna Cardoso Maciel, Francisco Felipe Bezerra, Paulo Antônio de Souza Mourão, Mauro Sérgio Gonçalves Pavão e Mariana Paranhos Stelling. "Extraction, Isolation, Characterization, and Biological Activity of Sulfated Polysaccharides Present in Ascidian Viscera Microcosmus exasperatus". Pharmaceuticals 16, n. 10 (3 ottobre 2023): 1401. http://dx.doi.org/10.3390/ph16101401.

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Ascidians are marine invertebrates that synthesize sulfated glycosaminoglycans (GAGs) within their viscera. Ascidian GAGs are considered analogues of mammalian GAGs and possess great potential as bioactive compounds, presenting antitumoral and anticoagulant activity. Due to its worldwide occurrence and, therefore, being a suitable organism for large-scale mariculture in many marine environments, our main objectives are to study Microcosmus exasperatus GAGs regarding composition, structure, and biological activity. We also aim to develop efficient protocols for sulfated polysaccharides extraction and purification for large-scale production and clinical applications. GAGs derived from M. exasperatus viscera were extracted by proteolytic digestion, purified by ion-exchange liquid chromatography, and characterized by agarose gel electrophoresis and enzymatic treatments. Anticoagulant activity was evaluated by APTT assays. Antitumoral activity was assessed in an in vitro model of tumor cell culture using MTT, clonogenic, and wound healing assays, respectively. Our results show that M. exasperatus presents three distinct polysaccharides; among them, two were identified: a dermatan sulfate and a fucosylated dermatan sulfate. Antitumoral activity was confirmed for the total polysaccharides (TP). While short-term incubation does not affect tumor cell viability at low concentrations, long-term TP incubation decreases LLC tumor cell growth/proliferation at different concentrations. In addition, TP decreased tumor cell migration at different concentrations. In conclusion, we state that M. exasperatus presents great potential as an alternative GAG source, producing compounds with antitumoral properties at low concentrations that do not possess anticoagulant activity and do not enhance other aspects of malignancy, such as tumor cell migration. Our perspectives are to apply these molecules in future preclinical studies for cancer treatment as antitumoral agents to be combined with current treatments to potentiate therapeutic efficacy.

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Jin, Xi-Feng, Gerald Spöttl, Julian Maurer, Svenja Nölting e Christoph Josef Auernhammer. "Inhibition of Wnt/β-Catenin Signaling in Neuroendocrine Tumors In Vitro: Antitumoral Effects". Cancers 12, n. 2 (4 febbraio 2020): 345. http://dx.doi.org/10.3390/cancers12020345.

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Background and aims: Inhibition of Wnt/β-catenin signaling by specific inhibitors is currently being investigated as an antitumoral strategy for various cancers. The role of Wnt/β-catenin signaling in neuroendocrine tumors still needs to be further investigated. Methods: This study investigated the antitumor activity of the porcupine (PORCN) inhibitor WNT974 and the β-catenin inhibitor PRI-724 in human neuroendocrine tumor (NET) cell lines BON1, QGP-1, and NCI-H727 in vitro. NET cells were treated with WNT974, PRI-724, or small interfering ribonucleic acids against β-catenin, and subsequent analyses included cell viability assays, flow cytometric cell cycle analysis, caspase3/7 assays and Western blot analysis. Results: Treatment of NET cells with WNT974 significantly reduced NET cell viability in a dose- and time-dependent manner by inducing NET cell cycle arrest at the G1 and G2/M phases without inducing apoptosis. WNT974 primarily blocked Wnt/β-catenin signaling by the dose- and time-dependent downregulation of low-density lipoprotein receptor-related protein 6 (LRP6) phosphorylation and non-phosphorylated β-catenin and total β-catenin, as well as the genes targeting the latter (c-Myc and cyclinD1). Furthermore, the WNT974-induced reduction of NET cell viability occurred through the inhibition of GSK-3-dependent or independent signaling (including pAKT/mTOR, pEGFR and pIGFR signaling). Similarly, treatment of NET cells with the β-catenin inhibitor PRI-724 caused significant growth inhibition, while the knockdown of β-catenin expression by siRNA reduced NET tumor cell viability of BON1 cells but not of NCI-H727 cells. Conclusions: The PORCN inhibitor WNT974 possesses antitumor properties in NET cell lines by inhibiting Wnt and related signaling. In addition, the β-catenin inhibitor PRI-724 possesses antitumor properties in NET cell lines. Future studies are needed to determine the role of Wnt/β-catenin signaling in NET as a potential therapeutic target.

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Stockert, J. C., M. Cañete, A. Villanueva, A. Juarranz, C. I. Trigoso e M. F. Braña. "Fluorescence of Chromatin DNA Induced by Antitumoral Naphthalimides". Zeitschrift für Naturforschung C 52, n. 5-6 (1 giugno 1997): 408–12. http://dx.doi.org/10.1515/znc-1997-5-621.

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Abstract Treatment of chicken blood smears and semithin sections from Epon-embedded mouse tissues with aqueous solutions of the 3-aminonaphthalimides FA-142, FA-2043, and FA-2143 induced a strong green-yellow fluorescence of chromatin under violet or violet-blue excitation. Chromatin emission was abolished by previous DNase or hot TCA treatment. The use of 3-methoxy (FA-655) and 3-nitro derivatives (M-4212 and M-12210) resulted in very weak fluorescence of chromatin. Absorption maxima at 346 and 408 nm and an emission peak at 570 nm were observed for the free compound FA-142. Fluorescence properties open new and interesting applications for some of these antitumoral and DNA-intercalating naphthalimides.

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Calvo-Martín, Gorka, Daniel Plano, Nuria Martínez-Sáez, Carlos Aydillo, Esther Moreno, Socorro Espuelas e Carmen Sanmartín. "Norbornene and Related Structures as Scaffolds in the Search for New Cancer Treatments". Pharmaceuticals 15, n. 12 (25 novembre 2022): 1465. http://dx.doi.org/10.3390/ph15121465.

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Abstract (sommario):

The norbornene scaffold has arisen as a promising structure in medicinal chemistry due to its possible therapeutic application in cancer treatment. The development of norbornene-based derivatives as potential chemotherapeutic agents is attracting significant attention. Here, we report an unprecedented review on the recent advances of investigations into the antitumoral efficacy of different compounds, including the abovementioned bicyclic scaffold in their structure, in combination with chemotherapeutic agents or forming metal complexes. The impact that structural modifications to these bicyclic compounds have on the antitumoral properties and the mechanisms by which these norbornene derivatives act are discussed in this review. In addition, the use of norbornene, and its related compounds, encapsulation in nanosystems for its use in cancer therapies is here detailed.

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Felthaus, Oliver, Simon Vedlin, Andreas Eigenberger, Silvan M. Klein e Lukas Prantl. "Exosomes from Adipose-Tissue-Derived Stem Cells Induce Proapoptotic Gene Expression in Breast Tumor Cell Line". International Journal of Molecular Sciences 25, n. 4 (12 febbraio 2024): 2190. http://dx.doi.org/10.3390/ijms25042190.

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Abstract (sommario):

Lipofilling is an option for breast reconstruction after tumor resection to avoid the complications of an implant-based reconstruction. Although some concerns exist regarding the oncological safety of tissue rich in mesenchymal stem cells with their proangiogenic and proliferation-supportive properties, there are also reports that adipose-tissue-derived stem cells can exhibit antitumoral properties. We isolated primary adipose-tissue-derived stem cells. Both conditioned medium and exosomes were harvested from the cell culture and used to treat the breast cancer cell line MCF-7. Cell viability, cytotoxicity, and gene expression of MCF-7 cells in response to the indirect co-culture were evaluated. MCF-7 cells incubated with exosomes from adipose-tissue-derived stem cells show reduced cell viability in comparison to MCF-7 cells incubated with adipose-tissue-derived stem-cell-conditioned medium. Expression of proapoptotic genes was upregulated, and expression of antiapoptotic genes was downregulated. The debate about the oncological safety of autologous fat grafting after tumor resection continues. Here, we show that exosomes from adipose-tissue-derived stem cells exhibit some antitumoral properties on breast cancer cell line MCF-7.

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Kraus, J., W. Blaschek e G. Franz. "Antitumoral and Immunological Properties of a β-1,3/1,6-Glucan fromPhytophthora parasitica". Planta Medica 54, n. 06 (dicembre 1988): 565. http://dx.doi.org/10.1055/s-2006-962565.

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32

Nocentini, G., F. Federici, M. Grifantini e A. Barzi. "Copper complex of a new ribonucleotide reductase inhibitor characterized by antitumoral properties". Pharmacological Research 25 (maggio 1992): 312–13. http://dx.doi.org/10.1016/1043-6618(92)90421-7.

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33

Wang, Edina, Maria Alba Sorolla, Priya Darshini Gopal Krishnan e Anabel Sorolla. "From Seabed to Bedside: A Review on Promising Marine Anticancer Compounds". Biomolecules 10, n. 2 (6 febbraio 2020): 248. http://dx.doi.org/10.3390/biom10020248.

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Abstract (sommario):

The marine environment represents an outstanding source of antitumoral compounds and, at the same time, remains highly unexplored. Organisms living in the sea synthesize a wide variety of chemicals used as defense mechanisms. Interestingly, a large number of these compounds exert excellent antitumoral properties and have been developed as promising anticancer drugs that have later been approved or are currently under validation in clinical trials. However, due to the high need for these compounds, new methodologies ensuring its sustainable supply are required. Also, optimization of marine bioactives is an important step for their success in the clinical setting. Such optimization involves chemical modifications to improve their half-life in circulation, potency and tumor selectivity. In this review, we outline the most promising marine bioactives that have been investigated in cancer models and/or tested in patients as anticancer agents. Moreover, we describe the current state of development of anticancer marine compounds and discuss their therapeutic limitations as well as different strategies used to overcome these limitations. The search for new marine antitumoral agents together with novel identification and chemical engineering approaches open the door for novel, more specific and efficient therapeutic agents for cancer treatment.

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Hernández, Ángela-Patricia, Laura Iglesias-Anciones, José Javier Vaquero-González, Rafael Piñol, Julio J. Criado, Emilio Rodriguez, Pablo Juanes-Velasco et al. "Enhancement of Tumor Cell Immunogenicity and Antitumor Properties Derived from Platinum-Conjugated Iron Nanoparticles". Cancers 15, n. 12 (15 giugno 2023): 3204. http://dx.doi.org/10.3390/cancers15123204.

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From chemistry design to clinical application, several approaches have been developed to overcome platinum drawbacks in antitumoral therapies. An in-depth understanding of intracellular signaling may hold the key to the relationship of both conventional drugs and nanoparticles. Within these strategies, first, nanotechnology has become an essential tool in oncotherapy, improving biopharmaceutical properties and providing new immunomodulatory profiles to conventional drugs mediated by activation of endoplasmic reticulum (ER) stress. Secondly, functional proteomics techniques based on microarrays have proven to be a successful method for high throughput screening of proteins and profiling of biomolecule mechanisms of action. Here, we conducted a systematic characterization of the antitumor profile of a platinum compound conjugated with iron oxide nanoparticles (IONPs). As a result of the nano-conjugation, cytotoxic and proteomics profiles revealed a significant improvement in the antitumor properties of the starting material, providing selectivity in certain tumor cell lines tested. Moreover, cell death patterns associated with immunogenic cell death (ICD) response have also been identified when ER signaling pathways have been triggered. The evaluation in several tumor cell lines and the analysis by functional proteomics techniques have shown novel perspectives on the design of new cisplatin-derived conjugates, the high value of IONPs as drug delivery systems and ICD as a rewarding approach for targeted oncotherapy and onco-immunotherapies.

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Rigon, Roberta Balansin, Márcia Helena Oyafuso, Andressa Terumi Fujimura, Maíra Lima Gonçalez, Alice Haddad do Prado, Maria Palmira Daflon Gremião e Marlus Chorilli. "Nanotechnology-Based Drug Delivery Systems for Melanoma Antitumoral Therapy: A Review". BioMed Research International 2015 (2015): 1–22. http://dx.doi.org/10.1155/2015/841817.

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Abstract (sommario):

Melanoma (MEL) is a less common type of skin cancer, but it is more aggressive with a high mortality rate. The World Cancer Research Fund International (GLOBOCAN 2012) estimates that there were 230,000 new cases of MEL in the world in 2012. Conventional MEL treatment includes surgery and chemotherapy, but many of the chemotherapeutic agents used present undesirable properties. Drug delivery systems are an alternative strategy by which to carry antineoplastic agents. Encapsulated drugs are advantageous due to such properties as high stability, better bioavailability, controlled drug release, a long blood circulation time, selective organ or tissue distribution, a lower total required dose, and minimal toxic side effects. This review of scientific research supports applying a nanotechnology-based drug delivery system for MEL therapy.

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Formagio, ASN, DD Ramos, MC Vieira, SR Ramalho, MM Silva, NAH Zárate, MA Foglio e JE Carvalho. "Phenolic compounds of Hibiscus sabdariffa and influence of organic residues on its antioxidant and antitumoral properties". Brazilian Journal of Biology 75, n. 1 (marzo 2015): 69–76. http://dx.doi.org/10.1590/1519-6984.07413.

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Abstract (sommario):

The aim of this study was to evaluate the phenolic and flavonoids contents and the antioxidant and antitumoral activity of leaf and calyx methanolic extracts from Hibiscus sabdariffa (roselle) cultivated with poultry litter and organosuper® under three modes of application. The total phenolic content in the each extract was determined using the Folin-Ciocalteu reagent and for aluminium chloride flavonoids. The antioxidant parameters were analyzed using a 2, 2-diphenyl-1-picrylhydrazyl (DPPH.) free radical scavenging assay. An antitumor colorimetric assay using sulforhodamine B. The highest contents of phenolic and flavonoids were observed in leaf extracts (389.98 and 104.52 mg g–1, respectively) and calyx extracts (474.09 and 148.35 mg g–1, respectively) from plants cultivated with organosuper®, although these values did not differ significantly from those observed for the other treatments. The average IC50 of leaves (43.48 μg mL–1) and calyces (37.15 μg mL–1) demonstrated that both have substances that may contribute to free radical scavenging action. The methanol extract from calyces showed significant selective activity against a leukemia line (K-562), with IC50 values of 0.12 mg mL–1 (organosuper®) and 1.16 mg mL–1 (poultry litter), with concentration-dependent, cytotoxic and cytocidal effects.

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Martínez-Iglesias, Olaia, Ivan Carrera, Vinogran Naidoo e Ramón Cacabelos. "AntiGan: An Epinutraceutical Bioproduct with Antitumor Properties in Cultured Cell Lines". Life 12, n. 1 (10 gennaio 2022): 97. http://dx.doi.org/10.3390/life12010097.

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Abstract (sommario):

Novel and effective chemotherapeutic agents are needed to improve cancer treatment. Epidrugs are currently used for cancer therapy but also exhibit toxicity. Targeting the epigenetic apparatus with bioproducts may aid cancer prevention and treatment. To determine whether the lipoprotein marine extract AntiGan shows epigenetic and antitumor effects, cultured HepG2 (hepatocellular carcinoma) and HCT116 (colorectal carcinoma) cell lines were treated with AntiGan (10, 50, 100, and to 500 µg/mL) for 24 h, 48 h, and 72 h. AntiGan (10 µg/mL) reduced cell viability after 48 h and increased Bax expression; AntiGan (10 and 50 µg/mL) increased caspase-3 immunoreactivity in HepG2 and HCT116 cells. AntiGan (10 and 50 µg/mL) attenuated COX-2 and IL-17 expression in both cell lines. AntiGan (10 µg/mL) increased 5mC levels in both cell types and reduced DNMT1 and DNMT3a expression in these cells. AntiGan (10 and 50 µg/mL) promoted DNMT3a immunoreactivity and reduced SIRT1 mRNA expression in both cell types. In HCT116 cells treated with AntiGan (10 µg/mL), SIRT1 immunoreactivity localized to nuclei and the cytoplasm; AntiGan (50 µg/mL) increased cytoplasmic SIRT1 localization in HCT116 cells. AntiGan is a novel antitumoral bioproduct with epigenetic properties (epinutraceutical) for treating liver and colorectal cancer.

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González-Ballesteros, Noelia, Immacolata Maietta, Raquel Rey-Méndez, M. Carmen Rodríguez-Argüelles, Mariano Lastra-Valdor, Antonella Cavazza, Maria Grimaldi, Franca Bigi e Rosana Simón-Vázquez. "Gold Nanoparticles Synthesized by an Aqueous Extract of Codium tomentosum as Potential Antitumoral Enhancers of Gemcitabine". Marine Drugs 21, n. 1 (27 dicembre 2022): 20. http://dx.doi.org/10.3390/md21010020.

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Abstract (sommario):

Cancer still poses a global threat, since a lot of tumors remain untreatable despite all the available chemotherapeutic drugs, whose side effects, it must also be noted, still raise concerns. The antitumoral properties of marine seaweeds make them a potential source of new, less toxic, and more active antitumoral agents. Furthermore, these natural extracts can be combined with nanotechnology to increase their efficacy and improve targeting. In this work, a Codium tomentosum (CT) aqueous extract was employed for the green synthesis of gold nanoparticles (Au@CT). The complete characterization of Au@CT was performed by UV-Vis spectroscopy, Fourier transform infrared (FTIR) spectroscopy, Zeta potential, electron microscopy, X-ray powder diffraction (XRD), high-performance steric exclusion chromatography (HPSEC), and by the determination of their antioxidant capacity. The antiproliferative activity of Au@CT was then tested in hepatic (HEPG-2) and pancreatic (BxPC-3) cell lines. Their potential capacity as enhancers of gemcitabine, a drug frequently used to treat both types of tumors, was also tested. The activity of Au@CT was compared to the activity of the CT extract alone. A synergistic effect with gemcitabine was proven for HEPG-2. Our results showed that gold nanoparticles synthesized from seaweed extracts with antitumoral activity could be a good gemcitabine enhancer.

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Teles, Amanda Mara, Leticia Prince Pereira Pontes, Sulayne Janayna Araújo Guimarães, Ana Luiza Butarelli, Gabriel Xavier Silva, Flavia Raquel Fernandes do Nascimento, Geusa Felipa de Barros Bezerra et al. "Marine-Derived Penicillium purpurogenum Reduces Tumor Size and Ameliorates Inflammation in an Erlich Mice Model". Marine Drugs 18, n. 11 (29 ottobre 2020): 541. http://dx.doi.org/10.3390/md18110541.

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Abstract (sommario):

Background: This study addresses the antitumoral properties of Penicillium purpurogenum isolated from a polluted lagoon in Northeastern Brazil. Methods: Ethyl Acetate Extracellular Extract (EAE) was used. The metabolites were studied using direct infusion mass spectrometry. The solid Ehrlich tumor model was used for antitumor activity. Female Swiss mice were divided into groups (n = 10/group) as follows: The negative control (CTL−), treated with a phosphate buffered solution; the positive control (CTL+), treated with cyclophosphamide (25 mg/kg); extract treatments at doses of 4, 20, and 100 mg/kg; animals without tumors or treatments (Sham); and animals without tumors treated with an intermediate dose (EAE20). All treatments were performed intraperitoneally, daily, for 15 days. Subsequently, the animals were euthanized, and the tumor, lymphoid organs, and serum were used for immunological, histological, and biochemical parameter evaluations. Results: The extract was rich in meroterpenoids. All doses significantly reduced tumor size, and the 20 and 100 mg/kg doses reduced tumor-associated inflammation and tumor necrosis. The extract also reduced the cellular infiltration of lymphoid organs and circulating TNF-α levels. The extract did not induce weight loss or renal and hepatic toxic changes. Conclusions: These results indicate that P. purpurogenum exhibits immunomodulatory and antitumor properties in vivo. Thus, fungal fermentation is a valid biotechnological approach to the production of antitumor agents.

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Alfaro, Ignacio, Margarita Vega, Carmen Romero e Maritza P. Garrido. "Mechanisms of Regulation of the Expression of miRNAs and lncRNAs by Metformin in Ovarian Cancer". Pharmaceuticals 16, n. 11 (24 ottobre 2023): 1515. http://dx.doi.org/10.3390/ph16111515.

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Abstract (sommario):

Ovarian cancer (OC) is one of the most lethal gynecological malignancies. The use of biological compounds such as non-coding RNAs (ncRNAs) is being considered as a therapeutic option to improve or complement current treatments since the deregulation of ncRNAs has been implicated in the pathogenesis and progression of OC. Old drugs with antitumoral properties have also been studied in the context of cancer, although their antitumor mechanisms are not fully clear. For instance, the antidiabetic drug metformin has shown pleiotropic effects in several in vitro models of cancer, including OC. Interestingly, metformin has been reported to regulate ncRNAs, which could explain its diverse effects on tumor cells. In this review, we discuss the mechanism of epigenetic regulation described for metformin, with a focus on the evidence of metformin-dependent microRNA (miRNAs) and long non-coding RNA (lncRNAs) regulation in OC.

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Zouari-Kessentini, Raoudha, Najet Srairi-Abid, Amine Bazaa, Mohamed El Ayeb, Jose Luis e Naziha Marrakchi. "Antitumoral Potential of Tunisian Snake Venoms Secreted Phospholipases A2". BioMed Research International 2013 (2013): 1–9. http://dx.doi.org/10.1155/2013/391389.

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Abstract (sommario):

Phospholipases type A2(PLA2s) are the most abundant proteins found in Viperidae snake venom. They are quite fascinating from both a biological and structural point of view. Despite similarity in their structures and common catalytic properties, they exhibit a wide spectrum of pharmacological activities. Besides being hydrolases, secreted phospholipases A2(sPLA2) are an important group of toxins, whose action at the molecular level is still a matter of debate. These proteins can display toxic effects by different mechanisms. In addition to neurotoxicity, myotoxicity, hemolytic activity, antibacterial, anticoagulant, and antiplatelet effects, some venom PLA2s show antitumor and antiangiogenic activities by mechanisms independent of their enzymatic activity. This paper aims to discuss original finding against anti-tumor and anti-angiogenic activities of sPLA2isolated from Tunisian vipers:Cerastes cerastesandMacrovipera lebetina, representing new tools to target specific integrins, mainly, and integrins.

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Andon, Fernando Torres, Alba Pensado-López, Clement Anfray, Aldo Ummarino, Iago Fernández-Mariño, Lucia Sanjurjo, Jose Crecente-Campo et al. "Abstract 715: Nanomedicines loaded with TLR agonists and inhibitors of immunosuppression to reprogram the tumor microenvironment". Cancer Research 84, n. 6_Supplement (22 marzo 2024): 715. http://dx.doi.org/10.1158/1538-7445.am2024-715.

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Abstract The stroma of solid tumors is populated by myeloid cells, which mostly represent macrophages. Tumor-associated macrophages (TAMs), strongly influenced by cancer cell-derived factors, are key drivers of immunosuppression and support tumor growth and spread to distant sites. Increasing evidence demonstrates their ability to hamper cancer patients' response to most treatments currently applied in the clinic, including immunotherapy. Therefore, strategies to counteract negative effects of TAMs are nowadays gaining momentum at preclinical, translational, and clinical levels. Here, we present the development and evaluation of nanoparticles (NPs) loaded with TLR agonists and/or inhibitors of immunosuppressive pathways to reprogram TAMs and the tumor microenvironment (TME) to unleash an effective immune response to fight against the tumor. Firstly, we have evaluated in vitro the ability of poly(I:C) and/or R848, agonists of TLR3 and TLR7/8 respectively, to reprogram TAMs into antitumor effector cells, and also the efficacy of Stattic and/or Galunisertib, inhibitors of STAT3 and TGF-β pathways respectively, to inhibit immunosuppression by cancer cells and/or TAMs. The best combinations of these drugs were encapsulated in nanoemulsions or polymeric nanocapsules for improved TAM-targeting and pharmacokinetics in vivo. These NPs were characterized for their physicochemical properties and also tested in vitro using primary human macrophages. For in vivo evaluation, subcutaneous and orthotopic murine models of lung cancer (CMT167) were used, showing antitumoral efficacy and TME reprogramming as evaluated by FACS, RNA analysis and multiplex immunofluorescence. Protamine-NCs-loaded with poly(I:C)+R848 and coated with an additional layer of hyaluronic acid functionalized with mannose were used to target the CD206 receptors, showing antitumoral efficacy mediated by TAM reprogramming, evaluated as higher CD86 while lower CD206 and Arg1 expression. Nanoemulsions with a PEGylated surfactant, encapsulating Stattic+Galunisertib+R848 showed faster antitumoral activity versus the free drugs. Experiments performed in IFN-γ KO mice and immune deficient mice (NSG and Balb/c nude) revealed that a fully functional immune system is crucial for the response to the treatment. In conclusion, our work demonstrates the antitumoral efficacy and reprogramming of the tumor microenvironment by combinations of TLR agonists and/or inhibitors of immunosuppression, which can be improved by nanotechnological approaches. Further investigations are ongoing to assess their antitumoral efficacy in other tumor models (i.e. breast and pancreatic cancer), with the final aim of clinical translation. Citation Format: Fernando Torres Andon, Alba Pensado-López, Clement Anfray, Aldo Ummarino, Iago Fernández-Mariño, Lucia Sanjurjo, Jose Crecente-Campo, Eduardo Fernández-Megía, Flavia Castro, Maria Jose Oliveira, Alfonso Calvo, Rosario García Campelo, Alberto Mantovani, Maria Jose Alonso, Paola Allavena. Nanomedicines loaded with TLR agonists and inhibitors of immunosuppression to reprogram the tumor microenvironment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 715.

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Rubel, Rosalia, Herta Stutz Dalla Santa, Leandro Freire dos Santos, Luiz Claudio Fernandes, Bonald Cavalcante Figueiredo e Carlos Ricardo Soccol. "Immunomodulatory and Antitumoral Properties of Ganoderma lucidum and Agaricus brasiliensis (Agaricomycetes) Medicinal Mushrooms". International Journal of Medicinal Mushrooms 20, n. 4 (2018): 393–403. http://dx.doi.org/10.1615/intjmedmushrooms.2018025979.

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Bovi, Michele, Maria E. Carrizo, Stefano Capaldi, Massimiliano Perduca, Laurent R. Chiarelli, Monica Galliano e Hugo L. Monaco. "Structure of a lectin with antitumoral properties in king bolete (Boletus edulis) mushrooms". Glycobiology 21, n. 8 (8 febbraio 2011): 1000–1009. http://dx.doi.org/10.1093/glycob/cwr012.

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Maillard, Sébastien, Juliette Gauduchon, Véronique Marsaud, Fabrice Gouilleux, Elisabeth Connault, Paule Opolon, Elias Fattal, Brigitte Sola e Jack-Michel Renoir. "Improved antitumoral properties of pure antiestrogen RU 58668-loaded liposomes in multiple myeloma". Journal of Steroid Biochemistry and Molecular Biology 100, n. 1-3 (luglio 2006): 67–78. http://dx.doi.org/10.1016/j.jsbmb.2006.03.008.

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Gimeno, M. Concepción, Helen Goitia, Antonio Laguna, M. Elvira Luque, M. Dolores Villacampa, Catarina Sepúlveda e Margarida Meireles. "Conjugates of ferrocene with biological compounds. Coordination to gold complexes and antitumoral properties". Journal of Inorganic Biochemistry 105, n. 11 (novembre 2011): 1373–82. http://dx.doi.org/10.1016/j.jinorgbio.2011.07.015.

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47

Mouhid, Lamia, Marta Gómez de Cedrón, Elena García-Carrascosa, Guillermo Reglero, Tiziana Fornari e Ana Ramírez de Molina. "Yarrow supercritical extract exerts antitumoral properties by targeting lipid metabolism in pancreatic cancer". PLOS ONE 14, n. 3 (26 marzo 2019): e0214294. http://dx.doi.org/10.1371/journal.pone.0214294.

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48

Dias, Paulo Fernando, Jarbas Mota Siqueira, Luiz Felipe Vendruscolo, Teresinha de Jesus Neiva, Antônio Ricardo Gagliardi, Marcelo Maraschin e Rosa Maria Ribeiro-do-Valle. "Antiangiogenic and antitumoral properties of a polysaccharide isolated from the seaweed Sargassum stenophyllum". Cancer Chemotherapy and Pharmacology 56, n. 4 (18 maggio 2005): 436–46. http://dx.doi.org/10.1007/s00280-004-0995-7.

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Carvalho Henriques, Magda, Maria Amparo F. Faustino e Susana Santos Braga. "Curcumin Innovative Delivery Forms: Paving the ‘Yellow Brick Road’ of Antitumoral Phytotherapy". Applied Sciences 10, n. 24 (16 dicembre 2020): 8990. http://dx.doi.org/10.3390/app10248990.

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Abstract (sommario):

This review deals with the various aspects involved in the medicinal action of curcumin, from the photosensitivity and its relevance to storage and shelf-life, to the different routes of administration, which influence the bioavailability. The focus of the review is on the antitumor properties of curcumin and the currently available solutions for their amelioration. The work starts by presenting a brief historical perspective on the origins and uses of curcumin, from early days until the present time. The following sections describe the physico-chemical properties of curcumin and their impact on the biological activity and pharmacokinetics, raising awareness to the need for formulations able to improve the bioavailability. The last section is focused on research efforts being made to circumvent curcumin’s instability and low availability due to the extensive hepatic first pass metabolism, describing innovative scientific advances and new patented formulations and emerging products on the market.

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Fathi, Faezeh, Samad N. Ebrahimi, Ana I. G. Valadão, Nelson Andrade, Anabela S. G. Costa, Cláudia Silva, Alireza Fathi et al. "Exploring Gunnera tinctoria: From Nutritional and Anti-Tumoral Properties to Phytosome Development Following Structural Arrangement Based on Molecular Docking". Molecules 26, n. 19 (30 settembre 2021): 5935. http://dx.doi.org/10.3390/molecules26195935.

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Abstract (sommario):

Gunnera tinctoria, an underexplored invasive plant found in Azores, Portugal, was studied regarding its nutritional, antioxidant, and antitumoral properties. Higher antioxidant activity was found in baby leaves, followed by adult leaves and inflorescences. A phenolic fraction of the plant was enriched using adsorbent resin column chromatography (DiaionTM HP20LX, and Relite EXA90). Antitumoral effects were observed with the enriched fractions in breast (MCF-7) and pancreatic (AsPC-1) cancer cell lines, being more pronounced in the latter. To improve protection and membrane absorption rates of phenolic compounds, nano-phytosomes and cholesterol-conjugated phytosomes coated with natural polymers were loaded with the enriched fraction. The particles were characterized, and their physiochemical properties were evaluated and compared. All samples presented anionic charge and nanometer size in relation to the inner layer and micrometer size regarding the external layers. In addition, the molecular arrangement of phenolics within both types of phytosomes were studied for the first time by molecular docking. Polarity and molecular size were key factors on the molecular arrangement of the lipid bilayer. In conclusion, G. tinctoria showed to be an interesting source of nutrients and phenolic compounds with anti-tumoral potential. Moreover, phytosome loading with these compounds can increase their stability and bioavailability having in view future applications.

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