Punicalagin and ellagic acid from pomegranate peel induce apoptosis and inhibits proliferation in human HepG2 hepatoma cells through targeting mitochondria

ABSTRACT Pomegranate peel polyphenols (PPPs) extracts presented anti-proliferation and apoptosis-inducing effects in human HepG2 hepatoma cells in our previous studies. This study aimed to investigate the differential anticancer effects of main PPPs components punicalagin (PC) and ellagic acid (EA) on HepG2 cells and their possible action mechanisms. Cell proliferation, morphology, cell cycle and apoptosis were investigated, and the results revealed that PC and EA mediated the cell-cycle arrest at the S-phase and G0/G1-phase and dose-dependently led to apoptosis in HepG2 cells. In addition, apoptosis-related protein activities and the reactive oxygen species levels showed that the activation of apoptosis-related proteins and the elevation of intracellular H2O2 production were aroused. It revealed that both PC and EA could inhibit cell growth and led to apoptosis in HepG2 cells, and PC was more effective than EA. Furthermore, one of the important apoptosis-inducing mechanisms is the participation of them in the mitochondrial apoptosis pathway. GRAPHICAL ABSTRAC