Phloridzin fatty acid esters induce apoptosis and alters gene expression in human liver cancer cells (261.2)

Abstract

Phloridzin Fatty Acid Esters Induce Apoptosis and Alters Gene Expression in Human Liver Cancer Cells Sandhya VG Nair, Ziaullah, HP Vasantha Rupasinghe*Department of Environmental Sciences, Faculty of Agriculture, Dalhousie University, Truro, NS B2N 5E3, Canada Abstract Phloridzin (phloretin 2‐O‐glucoside) is a dihydrochalcone, which is specifically found in apple and well known for its beneficial biological effects. To date, there is no report of antiproliferative effect of phloridzin on human cancer cell lines. We have synthesized novel acylated derivatives of phloridzin with six different long chain saturated, mono‐, and poly‐unsaturated fatty acids by regioselective enzymatic acylation. We investigated the effect of these six phloridzin fatty acid esters and their parent compounds on cell proliferation of hepatocellular carcinoma cells (HepG2) and its potential molecular mechanisms. Phloridzin fatty acid esters inhibited HepG2 cells growth in a concentration‐dependent manner by inducing apoptosis, as evidenced by decreased cell viability, formation of apoptotic bodies, decreased mitochondrial membrane potential, activation of caspase 3 and inhibition of DNA topoisomerases IIα activity that might induce G0/G1 phase arrest. However, phloridzin fatty acid esters did not significantly affect the growth of normal hepatocytes. Antiproliferative effect of phloridzin docosahexaenoic acid (DHA) ester was also associated with the down regulation of anti‐apoptotic genes, growth factor receptors, PI3k/AKT/mTOR as well as epigenetics regulators. Results reveal that phloridzin fatty acid esters possess potential as therapeutic agents for treating hepatocellular carcinoma.