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Atractylenolide II induces G1 cell-cycle arrest and apoptosis in B16 melanoma cells.
MedLine Citation:
PMID:  21524699     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
AIM OF THE STUDY: Atractylenolide II (AT-II) is a sesquiterpene compound isolated from the dried rhizome of Atractylodes macrocephala (Baizhu in Chinese), which is traditionally prescribed for melanoma treatment by Chinese medicine practitioners. Our previous study showed that AT-II can inhibit B16 cells proliferation. Here we investigated the mechanistic basis for the anti-proliferative activity of AT-II in B16 melanoma cells. MATERIALS AND METHODS: Cell viability was examined by MTT assay. Cell cycle distribution and apoptosis were determined by flow cytometry. Protein expression was determined by Western blotting. RESULTS: AT-II treatment for 48h dose-dependently inhibited cell proliferation with an IC(50) of 82.3μM, and induced G1 phase cell cycle arrest. Moreover, treatment with 75μM AT-II induced apoptosis. These observations were associated with the decrease of the expression of Cdk2, phosphorylated-Akt, phosphorylated-ERK and Bcl-2, the increase of the expression of phosphorylated-p38, phosphorylated-p53, p21, p27, and activation of caspases-8, -9 and -3. In addition, a chemical inhibitor of p53, PFTα, significantly decreased AT-II-mediated growth inhibition and apoptosis. CONCLUSIONS: We demonstrated that the G1-arresting and apoptotic effects of AT-II in B16 cells involve p38 activation and ERK inactivation, and the cytotoxic/apoptotic effects of AT-II are at least in part mediated by PI3K/Akt signaling and potentially p53 dependent. These findings provided chemical and pharmacological basis for the traditional application of Baizhu in melanoma treatment.
Authors:
Yan Ye; Hui Wang; Jian-Hong Chu; Gui-Xin Chou; Si-Bao Chen; Huanbiao Mo; Wang-Fun Fong; Zhi-Ling Yu
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-4-16
Journal Detail:
Title:  Journal of ethnopharmacology     Volume:  -     ISSN:  1872-7573     ISO Abbreviation:  -     Publication Date:  2011 Apr 
Date Detail:
Created Date:  2011-4-28     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7903310     Medline TA:  J Ethnopharmacol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2011. Published by Elsevier Ireland Ltd.
Affiliation:
Center for Cancer and Inflammation Research, School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong, China.
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