MP83-02 ADDITION OF EMETINE DIHYDROCHLORIDE TO PLATINUM BASED CHEMOTHERAPY INHIBITS BLADDER CANCER CELL PROLIFERATION AND REDUCES THE EFFECTIVE DOSE OF PLATINUM CHEMOTHERAPY

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You have accessJournal of UrologyBladder Cancer: Basic Research & Pathophysiology IV1 Apr 2016MP83-02 ADDITION OF EMETINE DIHYDROCHLORIDE TO PLATINUM BASED CHEMOTHERAPY INHIBITS BLADDER CANCER CELL PROLIFERATION AND REDUCES THE EFFECTIVE DOSE OF PLATINUM CHEMOTHERAPY Valerie J. Davidson, Robert H. Blackwell, Kimberly E. Foreman, Paul C. Kuo, Robert C. Flanigan, and Gopal N. Gupta Valerie J. DavidsonValerie J. Davidson More articles by this author , Robert H. BlackwellRobert H. Blackwell More articles by this author , Kimberly E. ForemanKimberly E. Foreman More articles by this author , Paul C. KuoPaul C. Kuo More articles by this author , Robert C. FlaniganRobert C. Flanigan More articles by this author , and Gopal N. GuptaGopal N. Gupta More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.2184AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Emetine is a natural alkaloid that inhibits protein synthesis at the micromolar level. Decades ago, Phase I and II clinical trials of emetine as a single agent showed modest efficacy against many solid tumors, but these findings were not pursued. We have previously reported that low, nanomolar concentrations of emetine act synergistically with cisplatin to inhibit invasive bladder cancer cell proliferation. Here, we extend these findings to evaluate the addition of emetine to the standard of care chemotherapeutic regimen of cisplatin plus gemcitabine. Because 50% of patients are unfit for cisplatin-based therapies, we also examined the effect of emetine combined with carboplatin and gemcitabine on bladder cancer cell proliferation. METHODS Normal urothelial cells and UMUC3, HT1376, and T24 invasive bladder cancer cell lines were cultured under standard conditions. Cells were treated with gemcitabine, cisplatin, carboplatin, and emetine alone or in combination at concentrations based on the drug's experimentally determined inhibitory concentration-50 (IC50). Proliferation was measured via MTT assay or trypan blue-staining based cell counts. Cell cycle data was obtained via DNA-propidium iodide staining and flow cytometry. RESULTS The addition of emetine to either cisplatin-gemcitabine or carboplatin-gemcitabine significantly decreased cell proliferation in cancer cells. Normal urothelial cells were more resistant with ten-fold higher concentrations of emetine required to observe the same effect on proliferation. Cell cycle analysis revealed the addition of emetine did not cause cell death, but rather induced a G1 growth arrest. This growth arrest was irreversible at cisplatin or carboplatin concentrations at or above the calculated IC50. CONCLUSIONS Addition of emetine to either cisplatin or carboplatin-based chemotherapeutic regimens resulted in a significant decrease in bladder cancer cell proliferation. Our findings suggest the addition of emetine to the current standard of care therapies may benefit patients. Importantly, inclusion of emetine appears to lower the dose of cisplatin or carboplatin required to block cell proliferation. This may allow some patients previously unfit for cisplatin-gemcitabine to qualify for this therapeutic regimen. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e1081 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Valerie J. Davidson More articles by this author Robert H. Blackwell More articles by this author Kimberly E. Foreman More articles by this author Paul C. Kuo More articles by this author Robert C. Flanigan More articles by this author Gopal N. Gupta More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...