The effect of glycolysis inhibitor dichloroacetate on the apoptosis rate and alteration of gene and miRNA expression of breast cancer cells MDA-MB-231

Gholami, Leila; Attari, Farnoosh; Talkhabi, Mahmood; Saadatpour, Fatemeh

The effect of glycolysis inhibitor dichloroacetate on the apoptosis rate and alteration of gene and miRNA expression of breast cancer cells MDA-MB-231

Authors

Leila Gholami ¹

Farnoosh Attari ¹

Mahmood Talkhabi ²

Fatemeh Saadatpour ³

¹ Department of Animal Biology, School of Biology, College of Science, University of Tehran, Tehran, Iran

² Faculty of Biological Sciences and Technology, Shahid Beheshti University, Tehran, Iran

³ Molecular Virology Lab, Department of Microbiology, School of Biology, College of Science, University of Tehran, Tehran, Iran

Abstract

Breast cancer is the most common cause of death from cancer among women. The triple-negative breast cancer (TNBC) is the most invasive subtype, and chemotherapy is the only therapy option. Cancer cells preferably utilize the glycolysis pathway even with proper oxygen availability, and this activation plays a great role in tumorigenesis. Therefore, glycolysis targeting can be an effective strategy for cancer treatment. Here, the apoptotic effect of a glycolysis inhibitor named dichloroacetate (DCA) on TNBC cells MDA-MB-231 was assessed, and the expression of anti-apoptotic genes and oncogenic miRNAs was evaluated. MTT assay showed that DCA reduces cell viability in a dose-dependent manner with the IC50 concentration of 50 mM. Annexin/PI assay demonstrated that DCA due to DCA treatment. Finally, the expression of anti-apoptotic genes Bcl2l1 and Mcl1 and oncogenic miRNAs miR21 and miR27a decreased due to DCA treatment. Our results confirmed that DCA, as a glycolysis inhibitor, leads to apoptosis induction in TNBC cells because of reducing expression of viability genes and miRNAs.

Keywords

Cell cycle

cell viability

metastasis

Oncogene

Triple-negative cancer

20.1001.1.24236330.1402.10.1.1.4

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