Resistomycin, a pentacyclic polyketide, inhibits the growth of triple negative breast cancer cells through induction of apoptosis and mitochondrial dysfunction

Abstract

Triple negative breast cancer (TNBC) stands among the most fatal and aggressive malignancies of women all over the world. This study was based on the screening of natural compounds library to identify potentially active entities against TNBC, which has been reported to be resistant towards currently available chemotherapeutics. A library of 100 compounds was screened against TNBC and non-TNBC breast cancer cell lines. Compounds that exhibited cytotoxicity and inhibited 80% growth of cancer cells at the concentration of 10μg/ml were considered as hits. 4 out of 100 screened compounds exhibited anti-proliferative potential against breast cancer while 2 out of 4 showed significant anti-cancer potential only against TNBC. In this article, we report the anti-cancer potential of resistomycin, a pentacyclic polyketide metabolite, which is isolated from bacterial strain Streptomyces spp. Resistomycin inhibited the growth of TNBC cells (MDA-MB231) more efficiently than non-TNBC (MCF-7) cells. Further, the molecular mechanism lying behind the anticancer potential of resistomycin was found to be induction of apoptosis and mitochondrial dysfunction. Resistomycin has significant potential to dissipate MMP to induce apoptosis in TNBC cells. The results of this research provide evidence to support this bioactive natural entity as an anti-TNBC drug candidate in future.