|Widdrol induces apoptosis via activation of AMP-activated protein kinase in colon cancer cells|
Authors: 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
Affiliations: Bioevaluation Center, Korea Research Institute of Bioscience and Biotechnology, Ochang, Cheongwon, Chungbuk 363-883, Republic of Korea, Department of Pharmacy, College of Pharmacy, Gachon University of Medicine and Science, Yeonsu, Incheon 406-799, Republic of Korea
Published online on: Thursday, January 19, 2012
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.