Compound K Induces Apoptosis via CAMK-IV/AMPK Pathways in HT-29 Colon Cancer Cells

被引:71
作者
Kim, Do Yeon [1 ]
Park, Min Woo [1 ]
Yuan, Hai Dan [1 ]
Lee, Hyo Jung [2 ]
Kim, Sung Hoon [2 ]
Chung, Sung Hyun [1 ]
机构
[1] Kyung Hee Univ, Coll Pharm, Dept Life & Nanopharmaceut Sci, Seoul 130701, South Korea
[2] Kyung Hee Univ, Coll Oriental Med, Canc Prevent Mat Dev Res Ctr, Seoul 130701, South Korea
关键词
Compound K; AMPK; CAMK-IV; apoptosis; HT-29 colon cancer cells; METABOLITE-INDUCED APOPTOSIS; GINSENG SAPONIN; PROTEIN-KINASE; INTESTINAL METABOLITE; UPSTREAM KINASE; CYTOCHROME-C; KEY SENSOR; ACTIVATION; AMPK; MITOCHONDRIA;
D O I
10.1021/jf902700h
中图分类号
S [农业科学];
学科分类号
09 ;
摘要
Although compound K (CK), an intestinal metabolite of ginseng protopanaxadiol saponins, has been known to induce apoptosis in various cancer cells, association of AMP-activated protein kinase (AMPK) with apoptosis in HT-29 colon cancer cells remains unclear. We hypothesized that CK may exert an anticancer activity through modulating the AMPK pathway in HT-29 cells. CK-induced apoptosis was associated with the disruption of the mitochondrial membrane potential, release of apoptogenic factors (cytochrome c and apoptosis-inducing factor) from mitochondria, and cleavage of caspase-9, caspase-3, caspase-8, Bid, and PARP proteins. This apoptotic effect of CK on colon cancer cells was found to be initiated by AMPK activation, and AMPK was activated through phosphorylation by Ca2+/calmodulin-activated protein kinase-IV (CAMK-IV). Treatment of HT-29 cells with compound C (AMPK inhibitor) or siRNA for AMPK completely abolished the CK-induced apoptosis. STO-609, CAMKs inhibitor, also attenuated CK-induced AMPK activation and apoptosis. In conclusion, the present study demonstrates that CK-mediated cell death of HT-29 colon cancer cells is regulated by CAMK-IV/AMPK pathways, and these findings provide a molecular basis for the anticancer effect of CK.
引用
收藏
页码:10573 / 10578
页数:6
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