Herbacetin induces apoptosis in HepG2 cells: Involvements of ROS and PI3K/Akt pathway

Herbacetin (HER) is a natural flavonoid compound that can be extracted from Ramose Scouring Rush Herb, and its biological and pharmacological activities lack of corresponding attention. In this study, the apoptotic effect of HER against the human hepatoma cell line (HepG2) was investigated. The results showed that HepG2 cells apoptosis occurred in a dose-dependent manner within 48 h incubated with HER, which was confirmed by DNA fragmentation, nuclear shrinkage, and poly (ADP-ribose) polymerase (PARP) cleavage. HER at 25-100 mu M induced a mitochondria-dependent apoptotic pathway associated with Bcl-2/Bax ratio decrease, mitochondrial membrane potential (Delta Psi) collapse, cytochrome c release, and caspase-3 activation. Increasing expression of peroxisome proliferator-activated receptor-gamma coactivator la (PGC-1 alpha) was also observed in HER-treated cells. Furthermore, the addition of a ROS inhibitor (N-Acetyl-L-cysteine, NAC) significantly attenuated the apoptosis induced by HER and also blocked the expression of PGC-1 alpha protein. Additionally, HER effectively inhibited the phosphorylation of Akt and the phosphatidylinositol-3 kinase (PI3K) inhibitor LY294002 increased the inhibition effect of HER on Akt phosphorylation. These findings provide evidences that HER induces HepG2 apoptosis in a ROS-mediated mitochondria-dependent manner that correlate with the inactivation of the PI3K/Akt pathway. Crown Copyright (C) 2012 Published by Elsevier Ltd. All rights reserved.