Patterns of cell death induced by metformin in human MCF-7 breast cancer cells.

Patterns of cell death induced by metformin in human MCF-7 breast cancer cells. Pathol Res Pract. 2020 Sep 06;216(11):153199 Authors: Dias Lopes NM, Marinello PC, Sanches LJ, da Silva Brito WA, Lovo-Martins MI, Pinge-Filho P, Luiz RC, Cecchini R, Cecchini AL Abstract The ability to evade apoptosis is an important mechanism of drug resistance and tumor progression in breast cancer. The induction of different pathways of cell death could be an important strategy to limit tumor progression. Metformin, a drug used to treat type two diabetes, has demonstrated promising results in breast cancer experiments. However, little is known about the patterns of cell death induced by this drug. We analyzed the involvement of apoptosis, necroptosis and ferroptosis in the toxicity of metformin in MCF-7 cells, evaluating proliferation, viability and oxidative stress. It was used different inhibitors of cell death: Z-VAD, a pan-caspase inhibitor that blocks apoptosis; Necrostatin-1, which inhibits RIPK1 activity and blocks necroptosis; and the iron chelator, deferoxamine, that chelates iron and prevents ferroptosis. The participation of oxidative stress was analyzed through the evaluation of total thiols, reduced glutathione (GSH) and malondialdehyde (MDA). Our results showed that metformin increased cell death, reduced proliferation, thiol and GSH and increased MDA in cells. After the association between metformin and Z-VAD or Necrostatin-1, the drug ...
Source: Pathology, Research and Practice - Category: Pathology Authors: Tags: Pathol Res Pract Source Type: research