Oncotarget

Research Papers:

Rottlerin inhibits cell growth and invasion via down-regulation of Cdc20 in glioma cells

Lixia Wang, Yingying Hou, Xuyuan Yin, Jingna Su, Zhe Zhao, Xiantao Ye, Xiuxia Zhou, Li Zhou and Zhiwei Wang _

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Oncotarget. 2016; 7:69770-69782. https://doi.org/10.18632/oncotarget.11974

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Abstract

Lixia Wang1, Yingying Hou1, Xuyuan Yin1, Jingna Su1, Zhe Zhao1, Xiantao Ye1, Xiuxia Zhou1, Li Zhou2, Zhiwei Wang1,3

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 Gynecologic Oncosurgery, Jilin Province Cancer Hospital, Changchun, Jilin, China

3Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, USA

Correspondence to:

Li Zhou, email: libyacynthia@163.com

Zhiwei Wang, email: zwang6@bidmc.harvard.edu

Keywords: rottlerin, Cdc20, glioma, growth, invasion

Received: June 30, 2016     Accepted: September 05, 2016     Published: September 12, 2016

ABSTRACT

Rottlerin, isolated from a medicinal plant Mallotus phillippinensis, has been demonstrated to inhibit cellular growth and induce cytoxicity in glioblastoma cell lines through inhibition of calmodulin-dependent protein kinase III. Emerging evidence suggests that rottlerin exerts its antitumor activity as a protein kinase C inhibitor. Although further studies revealed that rottlerin regulated multiple signaling pathways to suppress tumor cell growth, the exact molecular insight on rottlerin-mediated tumor inhibition is not fully elucidated. In the current study, we determine the function of rottlerin on glioma cell growth, apoptosis, cell cycle, migration and invasion. We found that rottlerin inhibited cell growth, migration, invasion, but induced apoptosis and cell cycle arrest. Mechanistically, the expression of Cdc20 oncoprotein was measured by the RT-PCR and Western blot analysis in glioma cells treated with rottlerin. We observed that rottlerin significantly inhibited the expression of Cdc20 in glioma cells, implying that Cdc20 could be a novel target of rottlerin. In line with this, over-expression of Cdc20 decreased rottlerin-induced cell growth inhibition and apoptosis, whereas down-regulation of Cdc20 by its shRNA promotes rottlerin-induced anti-tumor activity. Our findings indicted that rottlerin could exert its tumor suppressive function by inhibiting Cdc20 pathway which is constitutively active in glioma cells. Therefore, down-regulation of Cdc20 by rottlerin could be a promising therapeutic strategy for the treatment of glioma.


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