Abstract

CHEMOTHERAPEUTIC EFFICACY OF WITHAFERIN-A IN EXPERIMENTAL HEPATOCELLULAR CARCINOMA

Murugan Sivalingam*, Vishalbabu G.N., Ekambaram Ganapathy, Shruthy Sureshkumar, Lekha Veluthakunju, Deepak Kuttikatt Soman

ABSTRACT

Hepatocellular Carcinoma is the leading cause of death among men worldwide. Chemoprevention and chemotherapy play beneficial roles in reducing the incidence and mortality of cancer. Cancer cell metabolism is characterized by an enhanced uptake and utilization of glucose, a phenomenon known as the Warburg effect. The persistent activation of altered metabolic enzymes is considered to be fundamental to the transformation of normal cells to cancer cells. Accordingly, interrupting cancer promoting metabolic sites may provide a promising strategy to halt tumor development. Identifying the abnormalities of cellular energy metabolism facilitates early detection and management of liver cancer. In view above, we tried to demonstrate dysregulated and reprogrammed cancer metabolism followed by clinical relevance of the metabolic enzymes, such as Glycolytic enzymes, gluconeogenesis, TCA cycle enzymes and glycoproteins. The present study was evaluated to check the effect of withaferin-A on cellular metabolic energy fluxes in DEN induced proliferative liver cancer. The results showed that the activities of glycolytic enzymes significantly increased and gluconeogenesis, tricarboxylic acid (TCA) cycle enzymes activities decreased in DEN induced liver cancer bearing rats. These altered metabolic enzymes were significantly normalized in the withaferin-A treated group rats. Our data suggest that withaferin-A, may extend its chemotherapeutic effect through modulating the metabolic enzymes and glycoproteins, indicators of promising chemotherapeutic agent for cancer treatment.

Keywords: Withaferin-A, glycolysis, gluconeogenic enzymes, TCA cycle, liver cancer, DEN.