Emetine Dihydrochloride: A Novel Therapy for Bladder Cancer Journal Article

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Authors: Foreman, K. E.; Jesse, J. N., 3rd; Kuo, P. C.; Gupta, G. N.
Article Title: Emetine Dihydrochloride: A Novel Therapy for Bladder Cancer
Abstract: PURPOSE: Current cisplatin-based therapies for Stage IV bladder cancer have a 5-year survival of 4-20%, underscoring the need to develop novel therapies for these patients. Emetine dihydrochloride, a natural alkaloid, demonstrated modest anti-cancer efficacy as a single agent in clinical trials in the 1970's, but was not pursued. Recently, studies reported emetine induces apoptosis in leukemia cell lines, which was enhanced by cisplatin. We sought to determine the anti-proliferative effects of emetine with and without cisplatin on bladder cancer cells. MATERIALS AND METHODS: Human bladder cancer cell lines and normal human urothelial cell cultures were treated with emetine, cisplatin or both agents. Cell proliferation was measured, and synergy evaluated using the Chou-Talalay method and the combination index (CI) calculated. Cell cycle analysis and caspase activation were evaluated to assess growth arrest and apoptosis. RESULTS: Emetine and cisplatin each inhibited bladder cancer cell proliferation. When combined, emetine and cisplatin acted synergistically to inhibit tumor cell proliferation with CI values reflecting moderate to strong synergy. Normal urothelial cells were relatively resistant to the same treatment. Emetine alone and in combination with cisplatin appeared to primarily induce growth arrest, not apoptosis, of the tumor cells. CONCLUSIONS: This study demonstrates for the first time that emetine has in vitro anti-proliferative activity against bladder cancer cell lines at nanomolar concentrations, but had little effect on normal urothelial cells. Moreover, emetine and cisplatin worked synergistically to inhibit tumor cell proliferation. Our results suggest a combined therapy of emetine and cisplatin-based chemotherapy may benefit bladder cancer patients.
Journal Title: The Journal of urology
Volume: 191
Issue: 2
ISSN: 1527-3792; 0022-5347
Publisher: Elsevier Inc  
Date Published: 2014
Start Page: 502
End Page: 509
Language: ENG
DOI/URL:

10.1016/j.juro.2013.09.014

10.1016/j.juro.2013.09.014
Notes: CI: Copyright (c) 2014; JID: 0376374; 0 (Antineoplastic Agents); 0 (Protein Synthesis Inhibitors); EC 3.4.22.- (Caspase 3); EC 3.4.22.- (Caspase 8); Q20Q21Q62J (Cisplatin); X8D5EPO80M (Emetine); OTO: NOTNLM; 2013/09/09 [accepted]; 2013/09/14 [aheadofprint]; ppublish