Ginseng saponin metabolite induces apoptosis in MCF-7 breast cancer cells through the modulation of AMP-activated protein kinase

Previous studies have shown that the ginseng saponin metabolite, Compound K (20-O-d-glucopyranosyl-20(S)-protopanaxadiol, IH901), suppresses proliferation of various cancers and induces apoptosis. AMP-activated protein kinase (AMPK) is a sensor of cellular energy states and is involved in apoptosis of cancer cells. We hypothesized that Compound K may exert cytotoxicity in MCF-7 human breast cancer cells through modulation of AMPK, followed by a decrease in cyclooxygenase-2 (COX-2) expression. Compound K inhibited cell growth, induced apoptosis via generation of reactive oxygen species (ROS), as well as decreasing COX-2 expression and prostaglandin E(2) (PGE(2)) levels. These effects of Compound K were induced via an AMPK-dependent pathway and were abrogated by a specific AMPK inhibitor. These results suggest that Compound K induced apoptosis by modulating AMPK-COX-2 signaling in MCF-7 human breast cancer cells.