Investigating the Effect of EX-527 as SIRT1 Inhibitor in Breast Cancer Cell Line

Abstract

Background: Breast cancer is one of the most common malignant and metastatic tumors worldwide that cause death in women. Therefore, preventing the growth and metastasis of cancerous cells is essential for enhancing the prognosis and efficacy of treatment for breast cancer. Sirtuin 1 (SIRT1) is a nicotinamide-adenine dinucleotide (NAD+)-dependent deacetylase that has been linked to a number of biological processes, including genomic stability, cell cycle, cell survival and cancer metastasis. EX-527 is a selective and potent SIRT1 inhibitor. Recent studies have revealed that SIRT1 has an oncogenic role in breast cancer. Objective: To evaluate the effect of EX-527 on the MCF-7 breast cancer cell line. Methods: MCF-7 was cultured in complete DMEM and treated with and without EX-527. Cell viability of the breast cancer cell line was evaluated by MTT assay and apoptosis by Annexin V/PI staining. Migration and invasion of breast cancer cells were determined by wound healing and transwell invasion assays, respectively. Results: Results revealed that EX-527 at a concentration of 25.30 µM was associated with a significant anti-proliferative effect and induction of apoptosis (98.3%) in breast cancer cells. Treatment with EX-527 was also associated with significant suppression of migration and invasion of MCF-7. Conclusions: The current investigation showed that inhibition of SIRT1 by EX-527 inhibits proliferation, migration, invasion and apoptosis of human breast cancer cells.