Widdrol induces apoptosis via activation of AMP-activated protein kinase in colon cancer cells.

Widdrol, a natural sesquiterpene present in Juniperus sp., has been shown to exert anticancer and antifungal effects. Emerging evidence has suggested that AMP-activated protein kinase (AMPK), which functions as a cellular energy sensor, is a potential therapeutic target for human cancers. In this study, we found that AMPK mediates the anticancer effects of widdrol through induction of apoptosis in HT-29 colon cancer cells. We showed that widdrol induced the phosphorylation of AMPK in a dose- and time-dependent manner. The selective AMPK inhibitor compound C abrogated the inhibitory effect of widdrol on HT-29 cell growth. In addition, we demonstrated that widdrol induced apoptosis and this was associated with the activation of caspases, including caspase‑3/7 and caspase-9, in HT-29 cells. We also demonstrated that transfection of HT-29 cells with AMPK siRNAs significantly suppressed the widdrol-mediated apoptosis and the activation of caspases. However, cell cycle arrest induced by widdrol was not affected by transfection of HT-29 cells with AMPK siRNAs. Furthermore, widdrol inhibited HT-29 tumor growth in a human tumor xenograft model. Taken together, our results suggest that the anticancer effect of widdrol may be mediated, at least in part, by induction of apoptosis via AMPK activation.

Citation

Moo Rim Kang, Song-Kyu Park, Chang Woo Lee, Ig Jun Cho, Yeong Nang Jo, Jeong Wook Yang, Jin-Ah Kim, Jieun Yun, Ki Hoon Lee, Hyun Ju Kwon, Byung Woo Kim, Kiho Lee, Jong Soon Kang, Hwan Mook Kim. Widdrol induces apoptosis via activation of AMP-activated protein kinase in colon cancer cells. Oncology reports. 2012 May;27(5):1407-12

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PMID: 22266984

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