Asifa Khan
Jamia Millia Islamia, India
Title: Withaerin a induces metabolic crisis in breast cancer cell lines via decreasing c-myc expression: Potential therapeutic implication
Biography
Biography: Asifa Khan
Abstract
Reprogrammed glucose metabolism is considered as the hallmark of the cancer with immense therapeutic relevance. Witahferin A (WA), a withanolide isolated from Withania somnifera has been shown to exhibit anticancer activity. But the role of WA in cancer metabolism still remain elusive. In line with this, we assessed the effect of WA on breast cancer metabolism and its underlying regulatory pathway. Herein, we showed that WA decreases the glucose uptake, lactate production and ATP generation in different breast cancer cell lines via suppression of key glycolytic enzymes i.e. GLUT1, HK2 and PKM2. We identified, WA induced suppression of glycolytic enzymes was through c-myc signaling - one of the major regulator of glycolysis.
Moreover, WA treatment significantly resulted in reduced cell viability, biomass and colony forming ability of breast cancer cells. Silencing of c-myc resulted in reduced glucose uptake, lactate production and ATP generation validating that regulation of Warburg effect is mediated through c-myc. Highlighting the importance of c-myc in glycolysis. To further validate our in vitro findings we used METABRIC dataset of ~2000 breast tumors and employed Pathifier algorithm to determine the pathway deregulation of glycolysis in each patient and normal sample Notably, highest deregulation of glycolysis was observed in breast tumor compared to normal tissues and found to be associated with poor prognosis. Taken together, our results highlight the anti- carcinogenic effect of Withaferin A in modulating breast cancer metabolism and the clinical significance of glycolysis in general.