Polyphenol galangin induces the ROS and ER stress-mediated intrinsic and extrinsic apoptotic pathways towards human colon carcinoma HCT-116 cells

Abstract

A natural anti-oxidant galangin, a flavonoid compound rich in the root of galangal, has been proved to exert anti-proliferation and apoptosis induction towards various cancer cells. However, its activities and molecular mechanism against colorectal cancer cell lines (e.g. HCT-116) is still unclear. The aim of this study was to reveal the inhibition and apoptosis induction of galangin in the HCT-116 cells. The results of CCK-8 assay demonstrated that galangin at 20-160 μmol/L inhibited the HCT-116 cells growth in a dose-time-dependent manner. Galangin changed cell morphology, arrested cell cycle at G0/G1 phase, decreased mitochondrial membrane potential, increased intracellular reactive oxygen species (ROS) and Ca2+ and induced early apoptosis in the HCT-116 cells. Based on western blotting results, on one hand, galangin at 80-160 μmol/L up-regulated pro-apoptotic proteins expression such as AIF, PIG3, and Bax, and induced mitochondrial pathway by up-regulating the levels of cleaved caspase-8, cleaved caspase-7, cleaved caspase-9 and cleaved caspase-3, as well as cleavage of poly (ADP-ribose) polymerase (PARP). On the other hand, galangin also induced endoplasmic reticulum (ER) stress in the cell via up-regulation of CHOP and DR5 and then activation of caspase cascades. The results illustrated that galangin induced apoptosis towards the HCT-116 cells through the ROS- and ER stress-mediated both intrinsic and extrinsic apoptotic pathways.
 KEYWORDS: galangin; human colon carcinoma cells; apoptotic mechanism; reactive oxygen species; endoplasmic reticulum stress