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Cytotoxicity of metformin against HT29 colon cancer cells contributes to mitochondrial Sirt3 upregulation
Author(s) -
Khodaei Forouzan,
Hosseini Sayed M.,
Omidi Mahmoud,
Hosseini Seyede F.,
Rezaei Mohsen
Publication year - 2021
Publication title -
journal of biochemical and molecular toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.526
H-Index - 58
eISSN - 1099-0461
pISSN - 1095-6670
DOI - 10.1002/jbt.22662
Subject(s) - sirt3 , metformin , mitochondrion , apoptosis , mitochondrial ros , cancer cell , cancer research , reactive oxygen species , chemistry , cytotoxic t cell , downregulation and upregulation , cell culture , biology , microbiology and biotechnology , cancer , pharmacology , endocrinology , medicine , biochemistry , enzyme , insulin , sirtuin , in vitro , gene , nad+ kinase , genetics
Cancer and diabetes, the two mitochondria‐related diseases, have recently been linked to silent mating‐type information regulation 2 homolog 3 (SIRT3) activity irregularities. In this study, the effect of metformin, an antidiabetic with anticancer properties, has been evaluated on mitochondrial functionality markers, cell death pathways, and SIRT3 enzyme activity in the colon cancer cell line, HT‐29, and human embryonic kidney cells (HEK 293). HT‐29 cells were treated with metformin (5, 10, 20, 40, and 80 µM) for 24, 48, and 72 h for measuring the IC 50 concentration. Reactive oxygen species (ROS) production, apoptosis, mitochondrial membrane potential, SIRT3 activity, and expression were evaluated against the colon cancer cell line, HT‐29. Results indicated a higher ROS production at 6 than 12 h with metformin treatment. Metformin modified the mitochondrial membrane potential, resulting in cell death induction. Results from SIRT3 activity and expression showed that metformin increased its activity and expression in cancer cells. In conclusion, metformin in HT‐29 cells disturbed the mitochondrial activity via increased ROS levels and SIRT3 activity, and these rapid modifications may play a key role in its cytotoxic property.

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