Gambogenic acid induces G1 arrest via GSK3β-dependent cyclin D1 degradation and triggers autophagy in lung cancer cells

Xian Jun Yu, Simon Q B HAN*, Zhe Sheng Wen, Liang Ma, Jin Gao, Guang Biao Zhou

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

59 Citations (Scopus)

Abstract

Cyclin D1, an oncogenic G1 cyclin which can be induced by environmental carcinogens and whose over-expression may cause dysplasia and carcinoma, has been shown to be a target for cancer chemoprevention and therapy. In this study, we investigated the effects and underlying mechanisms of action of a polyprenylated xanthone, gambogenic acid (GEA) on gefitinib-sensitive and -resistant lung cancer cells. We found that GEA inhibited proliferation, caused G1 arrest and repressed colony-forming activity of lung cancer cells. GEA induced degradation of cyclin D1 via the proteasome pathway, and triggered dephosphorylation of GSK3β which was required for cyclin D1 turnover, because GSK3β inactivation by its inhibitor or specific siRNA markedly attenuated GEA-caused cyclin D1 catabolism. GEA induced autophagy of lung cancer cells, possibly due to activation of GSK3β and inactivation of AKT/mTOR signal pathway. These results indicate that GEA is a cyclin D1 inhibitor and a GSK3β activator which may have chemopreventive and therapeutic potential for lung cancer.

Original languageEnglish
Pages (from-to)185-194
Number of pages10
JournalCancer Letters
Volume322
Issue number2
DOIs
Publication statusPublished - 28 Sep 2012

Scopus Subject Areas

  • Oncology
  • Cancer Research

User-Defined Keywords

  • Autophagy
  • Cyclin D1
  • G1 arrest
  • Gambogenic acid
  • GSK3β
  • Lung cancer

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