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Atractylenolide II induces G1 cell-cycle arrest and apoptosis in B16 melanoma cells

Authors Ye, Yan; Wang, Hui; Chu, Jian-Hong; Chou, Gui-xin; Chen, Si-Bao; Mo, Huanbiao; Fong, Wang-fun; Yu, Zhi-Ling

Journal JOURNAL OF ETHNOPHARMACOLOGY , JUN 14 2011,1:136

DOI 10.1016/j.jep.2011.04.020 PubMed 21524699

Abstract Ethnopharmacological relevance: 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 investigate 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 48 h dose-dependently inhibited cell proliferation with an IC(50) of 82.3 mu M and induced G1 phase cell cycle arrest. Moreover, treatment with 75 mu M 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, PFT alpha, 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 as well as ERK and Akt inactivation, and the cytotoxic/apoptotic effects of AT-II are potentially p53 dependent. These findings provided chemical and pharmacological basis for the traditional application of Baizhu in melanoma treatment. (C) 2011 Elsevier Ireland Ltd. All rights reserved.

Species covered 白术 Atractylodes macrocephala