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

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Title
Widdrol induces apoptosis via activation of AMP-activated protein kinase in colon cancer cells
Author(s)
Moorim Kang; S K Park; Chang Woo Lee; Ig Jun Cho; Yeong Nang Jo; Jeong Wook Yang; Jin-Ah Kim; Ji Eun Yun; Ki Hoon Lee; H J Kwon; B W Kim; K Lee; Jong Soon Kang; H M Kim
Bibliographic Citation
Oncology Reports, vol. 27, no. 5, pp. 1407-1412
Publication Year
2012
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. -------------------------------------------------------------------------------- Reaxys Database Information|
Keyword
AMP-activated protein kinaseApoptosisColon cancerWiddrol
ISSN
1021-335X
Publisher
Spandidos Publ Ltd
DOI
http://dx.doi.org/10.3892/or.2012.1644
Type
Article
Appears in Collections:
Ochang Branch Institute > Division of National Bio-Infrastructure > Laboratory Animal Resource & Research Center > 1. Journal Articles
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