Rottlerin exerts its anti-tumor activity through inhibition of Skp2 in breast cancer cells
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Xuyuan Yin1,*, Yu Zhang2,*, Jingna Su1,*, Yingying Hou1, Lixia Wang1, Xiantao Ye1, Zhe Zhao1, Xiuxia Zhou1, Yali Li3, Zhiwei Wang1,4
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 Oncology, Guizhou People’s Hospital, Guizhou, China
3Department of Anesthesiology, Shenzhen People’s Hospital, Shenzhen Anesthesiology Engineering Center, The Second Clinical Medical College, Jinan University, Guangdong, China
4Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Cambridge, MA, USA
*These authors contributed equally to this work
Yali Li, email: [email protected]
Zhiwei Wang, email: [email protected]
Keywords: rottlerin, breast cancer, Skp2, invasion, apoptosis
Received: June 06, 2016 Accepted: August 15, 2016 Published: August 25, 2016
Studies have investigated the tumor suppressive role of rottlerin in carcinogenesis. However, the molecular mechanisms of rottlerin-induced anti-tumor activity are largely unclear. Skp2 (S-phase kinase associated protein 2) has been validated to play an oncogenic role in a variety of human malignancies. Therefore, inactivation of Skp2 could be helpful for the treatment of human cancers. In the current study, we explore whether rottlerin could inhibit Skp2 expression, leading to inhibition of cell growth, migration and invasion in breast cancer cells. We found that rottlerin treatment inhibited cell growth, induced apoptosis and cell cycle arrest. We also revealed that rottlerin suppressed cell migration and invasion in breast cancer cells. Mechanically, we observed that rottlerin significantly down-regulated the expression of Skp2 in breast cancer cells. Importantly, overexpression of Skp2 abrogated rottlerin-mediated tumor suppressive activity, whereas down-regulation of Skp2 enhanced rottlerin-triggered anti-tumor function. Strikingly, we identified that rottlerin exhibited its anti-tumor potential partly through inactivation of Skp2 in breast cancer. Our findings indicate that rottlerin could be a potential safe agent for the treatment of breast cancer.
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