Cytotoxicity of metformin against HT29 colon cancer cells contributes to mitochondrial Sirt3 upregulation. 2021

Forouzan Khodaei, and Sayed M Hosseini, and Mahmoud Omidi, and Seyede F Hosseini, and Mohsen Rezaei
College of Animal Science and Veterinary Medicine, Shanxi Agricultural University, Taigu, China.

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 IC50 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.

UI MeSH Term Description Entries
D008687 Metformin A biguanide hypoglycemic agent used in the treatment of non-insulin-dependent diabetes mellitus not responding to dietary modification. Metformin improves glycemic control by improving insulin sensitivity and decreasing intestinal absorption of glucose. (From Martindale, The Extra Pharmacopoeia, 30th ed, p289) Dimethylguanylguanidine,Dimethylbiguanidine,Glucophage,Metformin HCl,Metformin Hydrochloride,HCl, Metformin,Hydrochloride, Metformin
D008928 Mitochondria Semiautonomous, self-reproducing organelles that occur in the cytoplasm of all cells of most, but not all, eukaryotes. Each mitochondrion is surrounded by a double limiting membrane. The inner membrane is highly invaginated, and its projections are called cristae. Mitochondria are the sites of the reactions of oxidative phosphorylation, which result in the formation of ATP. They contain distinctive RIBOSOMES, transfer RNAs (RNA, TRANSFER); AMINO ACYL T RNA SYNTHETASES; and elongation and termination factors. Mitochondria depend upon genes within the nucleus of the cells in which they reside for many essential messenger RNAs (RNA, MESSENGER). Mitochondria are believed to have arisen from aerobic bacteria that established a symbiotic relationship with primitive protoeukaryotes. (King & Stansfield, A Dictionary of Genetics, 4th ed) Mitochondrial Contraction,Mitochondrion,Contraction, Mitochondrial,Contractions, Mitochondrial,Mitochondrial Contractions
D009363 Neoplasm Proteins Proteins whose abnormal expression (gain or loss) are associated with the development, growth, or progression of NEOPLASMS. Some neoplasm proteins are tumor antigens (ANTIGENS, NEOPLASM), i.e. they induce an immune reaction to their tumor. Many neoplasm proteins have been characterized and are used as tumor markers (BIOMARKERS, TUMOR) when they are detectable in cells and body fluids as monitors for the presence or growth of tumors. Abnormal expression of ONCOGENE PROTEINS is involved in neoplastic transformation, whereas the loss of expression of TUMOR SUPPRESSOR PROTEINS is involved with the loss of growth control and progression of the neoplasm. Proteins, Neoplasm
D003110 Colonic Neoplasms Tumors or cancer of the COLON. Cancer of Colon,Colon Adenocarcinoma,Colon Cancer,Cancer of the Colon,Colon Neoplasms,Colonic Cancer,Neoplasms, Colonic,Adenocarcinoma, Colon,Adenocarcinomas, Colon,Cancer, Colon,Cancer, Colonic,Cancers, Colon,Cancers, Colonic,Colon Adenocarcinomas,Colon Cancers,Colon Neoplasm,Colonic Cancers,Colonic Neoplasm,Neoplasm, Colon,Neoplasm, Colonic,Neoplasms, Colon
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D015854 Up-Regulation A positive regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins. Receptor Up-Regulation,Upregulation,Up-Regulation (Physiology),Up Regulation
D015971 Gene Expression Regulation, Enzymologic Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in enzyme synthesis. Enzymologic Gene Expression Regulation,Regulation of Gene Expression, Enzymologic,Regulation, Gene Expression, Enzymologic
D015972 Gene Expression Regulation, Neoplastic Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in neoplastic tissue. Neoplastic Gene Expression Regulation,Regulation of Gene Expression, Neoplastic,Regulation, Gene Expression, Neoplastic
D056566 Sirtuin 3 A sirtuin family member found primarily in MITOCHONDRIA. It is a multifunctional enzyme that contains a NAD-dependent deacetylase activity that is specific for HISTONES and a mono-ADP-ribosyltransferase activity. Silent Mating Type Information Regulation 2 Homolog 3,Sirt3
D019073 HT29 Cells Human colonic ADENOCARCINOMA cells that are able to express differentiation features characteristic of mature intestinal cells such as the GOBLET CELLS. HT-29 Cells,Cell, HT-29,Cell, HT29,Cells, HT-29,Cells, HT29,HT 29 Cells,HT-29 Cell,HT29 Cell

Related Publications

Forouzan Khodaei, and Sayed M Hosseini, and Mahmoud Omidi, and Seyede F Hosseini, and Mohsen Rezaei
June 2019, International journal of molecular sciences,
Forouzan Khodaei, and Sayed M Hosseini, and Mahmoud Omidi, and Seyede F Hosseini, and Mohsen Rezaei
May 2018, International journal of molecular sciences,
Forouzan Khodaei, and Sayed M Hosseini, and Mahmoud Omidi, and Seyede F Hosseini, and Mohsen Rezaei
August 2019, Biochemical and biophysical research communications,
Forouzan Khodaei, and Sayed M Hosseini, and Mahmoud Omidi, and Seyede F Hosseini, and Mohsen Rezaei
April 2013, Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine,
Forouzan Khodaei, and Sayed M Hosseini, and Mahmoud Omidi, and Seyede F Hosseini, and Mohsen Rezaei
January 2014, Chinese medical journal,
Forouzan Khodaei, and Sayed M Hosseini, and Mahmoud Omidi, and Seyede F Hosseini, and Mohsen Rezaei
December 1993, Diseases of the colon and rectum,
Forouzan Khodaei, and Sayed M Hosseini, and Mahmoud Omidi, and Seyede F Hosseini, and Mohsen Rezaei
May 2022, The Journal of nutritional biochemistry,
Forouzan Khodaei, and Sayed M Hosseini, and Mahmoud Omidi, and Seyede F Hosseini, and Mohsen Rezaei
July 2016, Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine,
Forouzan Khodaei, and Sayed M Hosseini, and Mahmoud Omidi, and Seyede F Hosseini, and Mohsen Rezaei
March 2006, Zhonghua yi xue za zhi,
Forouzan Khodaei, and Sayed M Hosseini, and Mahmoud Omidi, and Seyede F Hosseini, and Mohsen Rezaei
May 2020, International journal of molecular sciences,
Copied contents to your clipboard!