title: Atractylenolide II induces G1 cell-cycle arrest and apoptosis in B16 melanoma cells.
abstract: BACKGROUND
  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.
  
  
  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 μM, and induced G1 phase cell cycle arrest. Moreover, treatment with 75 μM 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 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.
authors.affiliation: Center for Cancer and Inflammation Research, School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Ye
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.forename: Jian-Hong
authors.initials: JH
authors.lastname: Chu
authors.forename: Gui-Xin
authors.initials: GX
authors.lastname: Chou
authors.forename: Si-Bao
authors.initials: SB
authors.lastname: Chen
authors.forename: Huanbiao
authors.initials: H
authors.lastname: Mo
authors.forename: Wang-Fun
authors.initials: WF
authors.lastname: Fong
authors.forename: Zhi-Ling
authors.initials: ZL
authors.lastname: Yu
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D031174:Atractylodes / Q000737:chemistry*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D016193:G1 Phase / Q000187:drug effects* / Q000502:physiology; D020128:Inhibitory Concentration 50; D007783:Lactones / Q000494:pharmacology* / Q000627:therapeutic use; D008546:Melanoma, Experimental / Q000188:drug therapy* / Q000378:metabolism; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use; D027343:Rhizome; D012717:Sesquiterpenes / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D007783:Lactones; D010936:Plant Extracts; D012717:Sesquiterpenes; C458582:atractylenolide II