title: Rottlerin exerts its anti-tumor activity through inhibition of Skp2 in breast cancer cells.
abstract: 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.
authors: The Cyrus Tang Hematology Center and Collaborative Innovation Center of Hematology, Jiangsu Institute of Hematology, The First Affiliated Hospital, Soochow University, Suzhou, China.
authors: Xuyuan
authors: X
authors: Yin
authors: Department of Oncology, Guizhou People's Hospital, Guizhou, China.
authors: Yu
authors: Y
authors: Zhang
authors: The Cyrus Tang Hematology Center and Collaborative Innovation Center of Hematology, Jiangsu Institute of Hematology, The First Affiliated Hospital, Soochow University, Suzhou, China.
authors: Jingna
authors: J
authors: Su
authors: The Cyrus Tang Hematology Center and Collaborative Innovation Center of Hematology, Jiangsu Institute of Hematology, The First Affiliated Hospital, Soochow University, Suzhou, China.
authors: Yingying
authors: Y
authors: Hou
authors: The Cyrus Tang Hematology Center and Collaborative Innovation Center of Hematology, Jiangsu Institute of Hematology, The First Affiliated Hospital, Soochow University, Suzhou, China.
authors: Lixia
authors: L
authors: Wang
authors: The Cyrus Tang Hematology Center and Collaborative Innovation Center of Hematology, Jiangsu Institute of Hematology, The First Affiliated Hospital, Soochow University, Suzhou, China.
authors: Xiantao
authors: X
authors: Ye
authors: The Cyrus Tang Hematology Center and Collaborative Innovation Center of Hematology, Jiangsu Institute of Hematology, The First Affiliated Hospital, Soochow University, Suzhou, China.
authors: Zhe
authors: Z
authors: Zhao
authors: The Cyrus Tang Hematology Center and Collaborative Innovation Center of Hematology, Jiangsu Institute of Hematology, The First Affiliated Hospital, Soochow University, Suzhou, China.
authors: Xiuxia
authors: X
authors: Zhou
authors: Department of Anesthesiology, Shenzhen People's Hospital, Shenzhen Anesthesiology Engineering Center, The Second Clinical Medical College, Jinan University, Guangdong, China.
authors: Yali
authors: Y
authors: Li
authors: The Cyrus Tang Hematology Center and Collaborative Innovation Center of Hematology, Jiangsu Institute of Hematology, The First Affiliated Hospital, Soochow University, Suzhou, China.|Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Cambridge, MA, USA.
authors: Zhiwei
authors: Z
authors: Wang
mesh_terms: D000098:Acetophenones / Q000494:pharmacology*; D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001578:Benzopyrans / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D015536:Down-Regulation; D005260:Female; D006801:Humans; D044786:S-Phase Kinase-Associated Proteins / Q000096:biosynthesis*
chemical_list: D000098:Acetophenones; D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D001578:Benzopyrans; D044786:S-Phase Kinase-Associated Proteins; C085746:rottlerin
keywords: Skp2; apoptosis; breast cancer; invasion; rottlerin