Exploring the effect of EX-527 as a selective SIRT1 inhibitor against MCF-7 breast cell line by modulating POLD1 activity
DOI:
https://doi.org/10.32947/ajps.v25i3.1204Keywords:
Breast Cancer, MCF-7, POLD1, p53, SIRT1 inhibitorAbstract
Breast cancer is the most prevalent tumor diagnosed in women and the second cause of death around the world. Therefore, improving the prognosis and effectiveness of treatment for breast cancer requires more studies to understand the underlying molecular mechanisms of its pathogenesis.
Sirtuin 1 is a NAD+-dependent class III histone deacetylase enzyme that is involved in metastasis, apoptosis, tumor growth, and other carcinogenesis pathways. The precise function of Sirtuin1 in relation to breast cancer is yet unknown, and its impact is still debatable. The purpose of this study was to examine the effect of sirtuin1 downregulation on the expression level of p53, the tumor suppressor protein, and on the DNA polymerase delta1 (POLD1), the gene encoding the catalytic and proofreading subunit p125 of DNA polymerase δ, in order to determine the significant function of sirtuin1 in breast cancer. The expression level of proteins was determined by the western blot method. The results of the current study revealed that downregulation of SIRT1by the EX-527 compound in MCF-7 breast cancer cell lines resulted in increased expression of p53 and decreased expression of POLD1. This study suggested that sirtuin1 co-operate with POLD1 in the molecular mechanism of breast cancer; therefore, SIRT1 could be a promising potential target for breast cancer treatment in the future.
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