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• W2008472353 abstract "You have accessJournal of UrologyBladder Cancer: Basic Research II1 Apr 2010979 SELECTIVE PROTECTION OF RENAL PROXIMAL TUBULE CELLS FROM CISPLATIN TOXICITY BY A NOVEL ANTIOXIDANT PEPTIDE James Rosoff, James Wysock, Jie Chen, Ryan Branski, Puneet Masson, Alison Masyr, Hazel Szeto, Dix Poppas, and Diane Felsen James RosoffJames Rosoff More articles by this author , James WysockJames Wysock More articles by this author , Jie ChenJie Chen More articles by this author , Ryan BranskiRyan Branski More articles by this author , Puneet MassonPuneet Masson More articles by this author , Alison MasyrAlison Masyr More articles by this author , Hazel SzetoHazel Szeto More articles by this author , Dix PoppasDix Poppas More articles by this author , and Diane FelsenDiane Felsen More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2010.02.1926AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Cisplatin inhibits cell proliferation via DNA intercalation. However, a major side effect of cisplatin is nephrotoxicity, which results from the deleterious effects of reactive oxygen species (ROS) on renal proximal tubules. Although oxidative stress can be attenuated by free radical scavengers, such compounds should not diminish the killing of bladder cancer cells by cisplatin. Here, an in vitro study was conducted investigating the effects of SS-31 (a novel mitochondrial-targeted antioxidant peptide) on cisplatin-induced effects on either bladder cancer cells or renal proximal tubule cells. METHODS A human bladder cancer cell line (HTB-4) was cultured and pre-treated with SS-31 [1-100 nM] for 2 hours. The cells were then incubated with cisplatin [5 - 100 μM] for 24 hours. Relative cytotoxicity was measured using a cell proliferation assay (MTS) and relative cell viability was measured via trypan blue exclusion assay. The same protocol was used with renal proximal tubule (HKC-8) cells. In addition, a fluorescence assay (DCF) was performed on HKC-8 cells to measure ROS generation. RESULTS The MTS assay demonstrated a significant dose-dependent killing of HTB-4 cells by cisplatin (5μM: 20%, 20 μM: 55% and 100 μM: 64% cell killing compared to controls, all p < 0.05). Using a therapeutic concentration of cisplatin [20 μM] in the presence of SS-31 at 3 different concentrations [1, 10 and 100 nM], there was no significant reduction in cell killing (51%, 56%, and 59%, respectively) compared to cisplatin alone. Cisplatin 20 μM also demonstrated a significant cytotoxic effect on HTB-4 cells as shown by trypan blue exclusion; there was no significant decrease in cell killing when SS-31 was used. In HKC-8 cells, the MTS assay showed a significant dose-dependent cytotoxicity of cisplatin (28% and 46% cytotoxicity for cisplatin 20 μM and 100 μM, respectively). Pre-treatment with SS-31, significantly reduced cell death in HKC-8 cells treated with 20 μM cisplatin. These results were confirmed via the trypan blue assay. Cisplatin also demonstrated a dose-dependent generation of ROS (11-49%, all p < 0.05). Except for the subtherapeutic dose of cisplatin [5 μM], ROS was significantly attenuated at all doses of SS-31 (ROS reduction 12-26%, all p < 0.01), though this effect was not dose-dependent. CONCLUSIONS SS-31, a free radical scavenger and mitochondrial protectant, reduces oxidative damage and killing of kidney proximal tubule cells by cisplatin without reducing cisplatin's ability to inhibit bladder cancer cell proliferation. New York, NY© 2010 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 183Issue 4SApril 2010Page: e380-e381 Advertisement Copyright & Permissions© 2010 by American Urological Association Education and Research, Inc.MetricsAuthor Information James Rosoff More articles by this author James Wysock More articles by this author Jie Chen More articles by this author Ryan Branski More articles by this author Puneet Masson More articles by this author Alison Masyr More articles by this author Hazel Szeto More articles by this author Dix Poppas More articles by this author Diane Felsen More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ..." @default.
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• W2008472353 title "979 SELECTIVE PROTECTION OF RENAL PROXIMAL TUBULE CELLS FROM CISPLATIN TOXICITY BY A NOVEL ANTIOXIDANT PEPTIDE" @default.
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