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

Authors
Kang, Moo RimPark, Song-KyuLee, Chang WooChoi, Ig JunJo, Yeong NangYang, Jeong WookKim, Jin-AhYun, JieunLee, Ki HoonKwon, Hyun JuKim, Byung WooLee, KihoKang, Jong SoonKim, Hwan Mook
Issue Date
5월-2012
Publisher
SPANDIDOS PUBL LTD
Keywords
widdrol; AMP-activated protein kinase; colon cancer; apoptosis
Citation
ONCOLOGY REPORTS, v.27, no.5, pp.1407 - 1412
Indexed
SCIE
SCOPUS
Journal Title
ONCOLOGY REPORTS
Volume
27
Number
5
Start Page
1407
End Page
1412
URI
https://scholar.korea.ac.kr/handle/2021.sw.korea/108613
DOI
10.3892/or.2012.1644
ISSN
1021-335X
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 si RNAs 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.
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