title: 20(S)-Ginsenoside Rg3-induced apoptosis in HT-29 colon cancer cells is associated with AMPK signaling pathway.
abstract: 20(S)-ginsenoside Rg3 [20(S)-Rg3)], one of the main constituents isolated from Panax ginseng, has been shown to have an anti-cancer effect and to induce apoptosis by interfering with several signaling pathways. However, the molecular mechanisms of AMP-activated protein kinase (AMPK) associated with apoptosis in HT-29 colon cancer cells remain unclear. In the present study, we investigated whether 20(S)-Rg3 exerts an anti-proliferative effect and induces apoptosis by modulating the AMPK signaling pathway in HT-29 cells. 20(S)-Rg3-treated cells displayed several apoptotic features, including DNA fragmentation, proteolytic cleavage of poly (ADP-ribose) polymerase (PARP) and morphological changes. 20(S)-Rg3 down-regulated the expression of anti-apoptotic protein B-cell CLL/lymphoma 2 (Bcl2), up-regulated the expression of pro-apoptotic protein of p53 and Bcl-2-associated X protein (Bax), and caused the release of mitochondrial cytochrome c, PARP, caspase-9 and caspase-3. However, 20(S)-Rg3-induced apoptosis was completely abolished in the presence of compound C (AMPK inhibitor) or small interfering RNA for AMPK (siAMPK). In addition, STO-609 (CaMKKβ inhibitor) attenuated 20(S)-Rg3-induced AMPK activation and apoptosis. These results suggest that 20(S)-Rg3-induced apoptosis in HT-29 cells is mediated via the AMPK signaling pathway, and that 20(S)-Rg3 is capable of inducing apoptosis in colon cancer.
authors.affiliation: Department of Life and Nanopharmaceutical Science, College of Pharmacy, Kyung Hee University, Seoul 130-701, Korea.
authors.forename: Hai-Dan
authors.initials: HD
authors.lastname: Yuan
authors.forename: Hai-Yan
authors.initials: HY
authors.lastname: Quan
authors.forename: Ya
authors.initials: Y
authors.lastname: Zhang
authors.forename: Sung Hoon
authors.initials: SH
authors.lastname: Kim
authors.forename: Sung-Hyun
authors.initials: SH
authors.lastname: Chung