Curcumin suppresses cell growth and invasion and induces apoptosis by down-regulation of Skp2 pathway in glioma cellsE

被引:67
作者
Wang, Lixia [1 ,2 ]
Ye, Xiantao [1 ,2 ]
Cai, Xingming [3 ]
Su, Jingna [1 ,2 ]
Ma, Renqiang [4 ]
Yin, Xuyuan [1 ,2 ]
Zhou, Xiuxia [1 ,2 ]
Li, Huabin [3 ,4 ]
Wang, Zhiwei [1 ,2 ]
机构
[1] Soochow Univ, Cyrus Tang Hematol Ctr, Affiliated Hosp 1, Suzhou, Peoples R China
[2] Soochow Univ, Collaborat Innovat Ctr Hematol, Affiliated Hosp 1, Jiangsu Inst Hematol, Suzhou, Peoples R China
[3] Sun Yat Sen Univ, Affiliated Hosp 1, Dept Geriatr, Guangzhou 510275, Guangdong, Peoples R China
[4] Sun Yat Sen Univ, Affiliated Hosp 1, Dept ENT Head & Neck Surg, Guangzhou 510275, Guangdong, Peoples R China
基金
中国国家自然科学基金;
关键词
curcumin; Skp2; glioma; growth; invasion; EPITHELIAL-MESENCHYMAL TRANSITION; IN-VITRO; CYCLE ARREST; CYTOPLASMIC LOCALIZATION; DEPENDENT REGULATION; SIGNALING PATHWAY; POOR-PROGNOSIS; INHIBITION; UBIQUITINATION; GLIOBLASTOMA;
D O I
10.18632/oncotarget.4090
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
收藏
页码:18027 / 18037
页数:11
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