Cyproheptadine exhibits antitumor activity in urothelial carcinoma cells by targeting GSK3β to suppress mTOR and β-catenin signaling pathways
作者： Hsiao-Yen Hsieh , Cheng-Huang Shen , Ru-Inn Lin , Yu-Min Feng , Shih-Yuan Huang
DOI: 10.1016/J.CANLET.2015.09.018
关键词: Apoptosis 、 Protein kinase B 、 Necrosis 、 Cell cycle checkpoint 、 Cell culture 、 PI3K/AKT/mTOR pathway 、 Cyproheptadine 、 Cancer research 、 Biology 、 In vivo
摘要: Cyproheptadine, a serotonin antagonist, has recently been reported to function as novel therapeutic agent by inhibiting PI3K/AKT signaling in several human cancers. However, the effect of cyproheptadine urothelial carcinoma (UC) never explored. In this study, we determined on growth five UC cell lines and an vivo xenograft model. The results showed that exerted inhibitory proliferation cells both vitro vivo. Cyproheptadine also induced cycle arrest G1 phase, subsequently followed apoptosis necrosis. underlying mechanisms were associated with reduction c-Myc, induction p21 p27, stabilization Rb expression. addition, suppression GSK3β/TSC2/mTOR pathway deregulation GSK3β/β-catenin observed cyproheptadine-treated cells. Furthermore, cyproheptadine-induced was ANGPTL4 expression activation caspase3 PARP Our experimental provide evidence is suitable for treatment UC.
elsevier.com
sci-hub.se 参考文章(49)
Christina Barbara Ching, Donna Elizabeth Hansel, Expanding therapeutic targets in bladder cancer: the PI3K/Akt/mTOR pathway. Laboratory Investigation. ,vol. 90, pp. 1406- 1414 ,(2010) , 10.1038/LABINVEST.2010.133
Ken Inoki, Hongjiao Ouyang, Tianqing Zhu, Charlotta Lindvall, Yian Wang, Xiaojie Zhang, Qian Yang, Christina Bennett, Yuko Harada, Kryn Stankunas, Cun-yu Wang, Xi He, Ormond A. MacDougald, Ming You, Bart O. Williams, Kun-Liang Guan, TSC2 Integrates Wnt and Energy Signals via a Coordinated Phosphorylation by AMPK and GSK3 to Regulate Cell Growth Cell. ,vol. 126, pp. 955- 968 ,(2006) , 10.1016/J.CELL.2006.06.055
Jose J. Mansure, Roland Nassim, Simone Chevalier, Joice Rocha, Eleonora Scarlata, Wassim Kassouf, Inhibition of Mammalian Target of Rapamycin as a Therapeutic Strategy in the Management of Bladder Cancer Cancer Biology & Therapy. ,vol. 8, pp. 2339- 2347 ,(2009) , 10.4161/CBT.8.24.9987
Yu-Min Feng, Chin-Wen Feng, Solomon Chih-Cheng Chen, Cheng-Da Hsu, Unexpected remission of hepatocellular carcinoma (HCC) with lung metastasis to the combination therapy of thalidomide and cyproheptadine: report of two cases and a preliminary HCC cell line study Case Reports. ,vol. 2012, ,(2012) , 10.1136/BCR-2012-007180
Maria Angeles HONRUBIA, Jesus RODRIGUEZ, Rosa DOMINGUEZ, Estrella LOZOYA, Francesc MANAUT, Julio A. SEIJAS, Maria Carmen VILLAVERDE, Jose M. CALLEJA, Maria Isabel CADAVID, Saul MAAYANI, Ferran SANZ, Maria Isabel LOZA, Synthesis, affinity at 5-HT2A, 5-HT2B and 5-HT2C serotonin receptors and structure-activity relationships of a series of cyproheptadine analogues. Chemical & Pharmaceutical Bulletin. ,vol. 45, pp. 842- 848 ,(1997) , 10.1248/CPB.45.842
Andis Graudins, Andrew Stearman, Betty Chan, Treatment of the serotonin syndrome with cyproheptadine Journal of Emergency Medicine. ,vol. 16, pp. 615- 619 ,(1998) , 10.1016/S0736-4679(98)00057-2
C. J. Sherr, Cancer Cell Cycles Science. ,vol. 274, pp. 1672- 1677 ,(1996) , 10.1126/SCIENCE.274.5293.1672
Lina Sabatino, Massimo Pancione, Carolina Votino, Tommaso Colangelo, Angelo Lupo, Ettore Novellino, Antonio Lavecchia, Vittorio Colantuoni, Emerging role of the β-catenin-PPARγ axis in the pathogenesis of colorectal cancer World Journal of Gastroenterology. ,vol. 20, pp. 7137- 7151 ,(2014) , 10.3748/WJG.V20.I23.7137
Chunming Liu, Yiming Li, Mikhail Semenov, Chun Han, Gyeong-Hun Baeg, Yi Tan, Zhuohua Zhang, Xinhua Lin, Xi He, Control of β-Catenin Phosphorylation/Degradation by a Dual-Kinase Mechanism Cell. ,vol. 108, pp. 837- 847 ,(2002) , 10.1016/S0092-8674(02)00685-2
Xinliang Mao, Sheng-ben Liang, Rose Hurren, Marcela Gronda, Sue Chow, G. Wei Xu, Xiaoming Wang, Reza Beheshti Zavareh, Nazir Jamal, Hans Messner, David W. Hedley, Alessandro Datti, Jeff L. Wrana, Yuanxiao Zhu, Chang-xin Shi, Kyle Lee, Rodger Tiedemann, Suzanne Trudel, A. Keith Stewart, Aaron D. Schimmer, Cyproheptadine displays preclinical activity in myeloma and leukemia. Blood. ,vol. 112, pp. 760- 769 ,(2008) , 10.1182/BLOOD-2008-02-142687