1. Metformin pretreatment reduces effect to dacarbazine and suppresses melanoma cell resistance.
- Author
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Sanches LJ, Marinello PC, da Silva Brito WA, Lopes NMD, Luiz RC, Cecchini R, and Cecchini AL
- Subjects
- 8-Hydroxy-2'-Deoxyguanosine metabolism, Animals, Cell Line, Tumor, Malondialdehyde metabolism, Melanoma, Experimental metabolism, Melanoma, Experimental pathology, Mice, NF-E2-Related Factor 2 metabolism, NF-kappa B metabolism, Oxidative Stress drug effects, Skin Neoplasms metabolism, Skin Neoplasms pathology, Tumor Suppressor Protein p53 metabolism, Antineoplastic Agents, Alkylating pharmacology, Antioxidants pharmacology, Dacarbazine pharmacology, Drug Resistance, Neoplasm drug effects, Melanoma, Experimental drug therapy, Metformin pharmacology, Skin Neoplasms drug therapy
- Abstract
Oxidative stress role on metformin process of dacarbazine (DTIC) inducing resistance of B16F10 melanoma murine cells are investigated. To induce resistance to DTIC, murine melanoma cells were exposed to increasing concentrations of dacarabazine (DTIC-res group). Metformin was administered before and during the induction of resistance to DTIC (MET-DTIC). The oxidative stress parameters of the DTIC-res group showed increased levels of malondialdehyde (MDA), thiol, and reduced nuclear p53, 8-hydroxy-2'-deoxyguanosine (8-OH-DG), nuclear factor kappa B (NF-ĸB), and Nrf2. In presence of metformin in the resistant induction process to DTIC, (MET-DTIC) cells had increased antioxidant thiols, MDA, nuclear p53, 8-OH-DG, Nrf2, and reducing NF-ĸB, weakening the DTIC-resistant phenotype. The exclusive administration of metformin (MET group) also induced the cellular resistance to DTIC. The MET group presented high levels of total thiols, MDA, and reduced percentage of nuclear p53. It also presented reduced nuclear 8-OH-DG, NF-ĸB, and Nrf2 when compared with the control. Oxidative stress and the studied biomarkers seem to be part of the alterations evidenced in DTIC-resistant B16F10 cells. In addition, metformin administration is able to play a dual role according to the experimental protocol, preventing or inducing a DTIC-resistant phenotype. These findings should help future research with the aim of investigating DTIC resistance in melanoma., (© 2021 International Federation for Cell Biology.)
- Published
- 2022
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