Licochalcone A from licorice root, an inhibitor of human hepatoma cell growth via induction of cell apoptosis and cell cycle arrest

Abstract

We investigated the anti-cancer activity of Licochalcone A (LCA), extracted from licorice root. LCA inhibited the proliferation of HepG₂ cells with IC₅₀ (65.96 μM) for 24 h and IC₅₀ (44.13 μM) for 48 h and caused significant morphological changes and also led to intracellular ROS generation. LCA affected HepG₂ cell growth by terminating cell cycle development at G2/M transition and further induced the apoptosis process. The mRNA expression of genes involved in cell cycles such as Survivin, Cyclin B1, and CDK1 were reduced; while, Weel, P21, Cyclin D1, and JNK1 showed increased mRNA expression. Two pathways consisting of internal and external factors were responsible for LCA -induced apoptosis. The anti-cancer action involved increased mRNA expression of DR3, DR5, caspases-3, caspases-8, caspases-10, Fas, Bad, Bax, Bcl-2, Bak, and PUMA; besides, decreased level of PKCε, p70S6K, and Akt. This study provides mechanistic explanation for anti-cancer activity of LCA and also suggests its potential role in the treatment of hepatoma cancer.

Keywords: Apoptosis; Death receptor pathway; HepG(2) cells; Licochalcone A; Mitochondrial pathway.