title: Widdrol induces apoptosis via activation of AMP-activated protein kinase             in colon cancer cells.
abstract: 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.
authors.affiliation: Bioevaluation Center, Korea Research Institute of Bioscience                     and Biotechnology, Ochang, Cheongwon, Chungbuk 363-883, Republic of Korea.
authors.forename: Moo Rim
authors.initials: MR
authors.lastname: Kang
authors.forename: Song-Kyu
authors.initials: SK
authors.lastname: Park
authors.forename: Chang Woo
authors.initials: CW
authors.lastname: Lee
authors.forename: Ig Jun
authors.initials: IJ
authors.lastname: Cho
authors.forename: Yeong Nang
authors.initials: YN
authors.lastname: Jo
authors.forename: Jeong Wook
authors.initials: JW
authors.lastname: Yang
authors.forename: Jin-Ah
authors.initials: JA
authors.lastname: Kim
authors.forename: Jieun
authors.initials: J
authors.lastname: Yun
authors.forename: Ki Hoon
authors.initials: KH
authors.lastname: Lee
authors.forename: Hyun Ju
authors.initials: HJ
authors.lastname: Kwon
authors.forename: Byung Woo
authors.initials: BW
authors.lastname: Kim
authors.forename: Kiho
authors.initials: K
authors.lastname: Lee
authors.forename: Jong Soon
authors.initials: JS
authors.lastname: Kang
authors.forename: Hwan Mook
authors.initials: HM
authors.lastname: Kim
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001567:Benzocycloheptenes / Q000008:administration & dosage / Q000494:pharmacology*; D020169:Caspases / Q000378:metabolism; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000201:enzymology*; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D010766:Phosphorylation / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D001567:Benzocycloheptenes; C078670:widdrol; D055372:AMP-Activated Protein Kinases; D020169:Caspases