Abstract 4561: The antihistamine cyproheptadine induces cell apoptosis through inhibition of β-catenin signaling pathways in urothelial carcinoma

Abstract

Abstract Recent studies have revealed that the cyproheptadine is a novel therapeutic agent for the treatment of malignancy, such as myeloma, leukemia and HCC. However, its effect on urothelial carcinoma cell is still unknown. The aim of this study was to investigate the effect and underline mechanism of cyproheptadine on UC. We used cell viability assay to investigate the drug effect on two UC cell lines, TSGH8301 and BFTC905, and found the IC50 which was about 55 μM. After treatment of cyproheptadine, cell cycle and apoptosis status of the UC cells were determined by flow cytometry and indicated cell cycle arrest in G0/G1 phase and induction of apoptosis. We further investigated the mechanism of the drug effect using western blot analysis and found that cyproheptadine induced downregulation of cyclin-D1 and c-Myc expression through the inhibition of β-catenin signaling pathway in UC cells. More importantly, Inhibition of β-catenin signaling pathway was related to downregulation of CCRK protein in TSGH8301 cell line, but through activation of IDAX protein leading to inhibition of β-catenin signaling pathway in BFTC905 cell line. These novel results demonstrated that cyproheptadine suppressed the β-catenin signaling pathway and induced UC cell apoptosis. Citation Format: Hsiao-Yen Hsieh, Yuan-Hung Wang, Cheng-Huang Shen, Shiu-Yi Chen, Michael Wy Chan, Cheng-Da Hsu. The antihistamine cyproheptadine induces cell apoptosis through inhibition of β-catenin signaling pathways in urothelial carcinoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4561. doi:10.1158/1538-7445.AM2014-4561