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

Yu, Xian-Jun, Han, Quan-Bin, Wen, Zhe-Sheng, Ma, Liang, Gao, Jin, and Zhou, Guang-Biao (2012) Gambogenic acid induces G1 arrest via GSK3β-dependent cyclin D1 degradation and triggers autophagy in lung cancer cells. Cancer Letters, 322 (2). pp. 185-194.

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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, gambogenicacid (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.

Item ID: 21989
Item Type: Article (Refereed Research - C1)
Keywords: lung cancer; gambogenic acid; G1 arrest; cyclin D1; GSK3β; autophagy
ISSN: 1872-7980
Date Deposited: 20 Jun 2012 01:04
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1112 Oncology and Carcinogenesis > 111205 Chemotherapy @ 100%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920102 Cancer and Related Disorders @ 100%
Citation Count from Web of Science Web of Science 2
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