ERK/GSK3β signaling is involved in atractylenolide I-induced apoptosis and cell cycle arrest in melanoma cells

Yan Ye, Xiao Juan Chao, Jin Feng Wu, Brian Chi Yan Cheng, Tao Su, Xiuqiong FU, Ting Li, Hui Guo, Anfernee K W TSE, Hiu Yee KWAN, Juan Du, Gui Xin Chou, Zhiling YU*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

12 Citations (Scopus)

Abstract

Novel agents need to be developed to overcome the limitations of the current melanoma therapeutics. Atractylenolide I (AT-I) is a sesquiterpene compound isolated from atractylodis macrocephalae rhizoma. Previous findings demonstrated that AT-I exhibited cytotoxic action in melanoma cells. However, the molecular mechanisms of AT-1's anti-melanoma properties remain to be elucidated. In the present study, the cell cycle-arrest and apoptosis-promoting effects as well as the ERK/GSK3β signaling-related mechanism of action of AT-I were examined. B16 melanoma cells were treated with various concentrations of AT-1 (50, 75 and 100 μM) for 48 or 72 h. Cell cycle and apoptosis were analyzed by flow cytometry. Protein expression levels were detected by western blot analysis. AT-I treatment induced G1 phase arrest, which was accompanied by increased p21 and decreased CDK2 protein expression levels. Apoptosis was observed after AT-I treatment for 72 h, which was accompanied by activated caspase-3 and -8. AT-I treatment significantly decreased phospho-ERK, phospho-GSK3β, c-Jun and increased p53 protein expression levels. Lithium chloride (LiCl, 5 mM), a GSK3β inhibitor, treatment alone did not increase the apoptosis of B16 cells, while pretreatment with LiCl markedly reversed AT-I-induced apoptosis. Additionally, AT-I-induced G1 phase arrest was partially reversed by LiCl pretreatment. In conclusion, ERK/GSK3β signaling was involved in the apoptotic and G1 phase arrest effects of AT-I in melanoma cells.

Original languageEnglish
Pages (from-to)1543-1548
Number of pages6
JournalOncology Reports
Volume34
Issue number3
DOIs
Publication statusPublished - 1 Sep 2015

Scopus Subject Areas

  • Oncology
  • Cancer Research

User-Defined Keywords

  • Apoptosis
  • Atractylenolide I
  • Cell cycle
  • ERK
  • GSK3β
  • Melanoma

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