Curcumin suppresses cell growth and invasion and induces apoptosis by down-regulation of Skp2 pathway in glioma cells
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Lixia Wang1,*, Xiantao Ye1,*, Xingming Cai2,*, Jingna Su1, Renqiang Ma3, Xuyuan Yin1, Xiuxia Zhou1, Huabin Li2,3, Zhiwei Wang1
1The Cyrus Tang Hematology Center and Collaborative Innovation Center of Hematology, Jiangsu Institute of Hematology, The First Affiliated Hospital, Soochow University, Suzhou, China
2Department of Geriatrics, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
3Department of ENT, Head and Neck Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
*These authors have contributed equally to this work
Zhiwei Wang, e-mail: [email protected]
Huabin Li, e-mail: [email protected]
Keywords: curcumin, Skp2, glioma, growth, invasion
Received: March 23, 2015 Accepted: May 11, 2015 Published: May 23, 2015
Studies have demonstrated that curcumin exerts its tumor suppressor function in a variety of human cancers including glioma. However, the exact underlying molecular mechanisms remain obscure. Emerging evidence has revealed that Skp2 (S-phase kinase associated protein 2) plays an oncogenic role in tumorigenesis. Therefore, we aim to determine whether curcumin suppresses the Skp2 expression, leading to the inhibition of cell growth, invasion, induction of apoptosis, and cell cycle arrest. To this end, we conducted multiple methods such as MTT assay, Flow cytometry, Wound healing assay, invasion assay, RT-PCR, Western blotting, and transfection to explore the functions and molecular insights of curcumin in glioma cells. We found that curcumin significantly inhibited cell growth, suppressed cell migration and invasion, induced apoptosis and cell cycle arrest in glioma cells. Furthermore, we observed that overexpression of Skp2 promoted cell growth, migration, and invasion, whereas depletion of Skp2 suppressed cell growth, migration, and invasion and triggered apoptosis in glioma cells. Mechanistically, we defined that curcumin markedly down-regulated Skp2 expression and subsequently up-regulated p57 expression. Moreover, our results demonstrated that curcumin exerts its antitumor activity through inhibition of Skp2 pathway. Collectively, our findings suggest that targeting Skp2 by curcumin could be a promising therapeutic approach for glioma prevention and therapy.
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