248 APOCYNIN AND DIPHENYLENE IODIUM(DPI) FUNCTION AS INHIBITORS OF CELL MIGRATION, AND PROLIFERATION BUT DO NOT INHIBIT NADPH OXIDASE IN RENAL CELLS CARCINOMA

You have accessJournal of UrologyKidney Cancer: Basic Research1 Apr 2011248 APOCYNIN AND DIPHENYLENE IODIUM(DPI) FUNCTION AS INHIBITORS OF CELL MIGRATION, AND PROLIFERATION BUT DO NOT INHIBIT NADPH OXIDASE IN RENAL CELLS CARCINOMA Jung-Sik Huh, Fernando J. Kim, Hyeon Ju Kim, and Hari Koul Jung-Sik HuhJung-Sik Huh Aurora, CO More articles by this author , Fernando J. KimFernando J. Kim Aurora, CO More articles by this author , Hyeon Ju KimHyeon Ju Kim Aurora, CO More articles by this author , and Hari KoulHari Koul Aurora, CO More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.02.317AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Renal cell carcinoma, which forms in tubules of the kidney, accounts for approximately 3% of adult malignancies and 90-95% of neoplasms arising from the kidney. Reactive oxygen species(ROS), which originate mainly from NADPH oxidase and are highly reactive O2 metabolites, have physiological and pathological processes. ROX and the oxidative stress have been associated with tumor formation. To respond oxidative stress, inhibition of NADPH oxidase represents a target for the treatment of many diseases. DPI and apocynin has been used as an efficient inhibitor of the complex NADPH oxidase in phagocytic and non-phagocytic cells. We investigated the effects of NOX4 inhibitors in renal cell carcinoma. METHODS We tested the effects of Apocynin and DPI against RCC cell lines (A498, Caki-2, KIKO-12), and the underlying mechanisms. Western Blot analysis was used to measure protein levels of Nox4, Akt and Erk signal molecules. Fluoremetric assays were used to measure ROS generation as well as NADPH oxidase activities. Cell growth and viability as well as migration were measured by standard methods. RESULTS Results show that treatment of RCC cells with apocynin and DPI resulted in a dose and time dependent inhibition of cell growth and proliferation. These treatments however did not induce apoptosis. Apocynin or DPI treatment had no effect on ROS (hydrogen peroxide and superoxide anion) generation in RCC cells. No changes were observed in NOX4, Akt, and Erk signal protein expression or activity change in the presence of apocynin and DPI. But apocynin and DPI interrupted and decreased cell migration of RCC cells. There was no change of actin cytoskeleton in treated and untreated A498 renal cell cancer cell line. CONCLUSIONS Apocynin and DPI, so called specific inhibitors of NADPH oxidase system acts as inhibitors of migration and proliferation but these effects are independent of NADPH oxidase inhibition in RCC cells as these agents did not inhibit Nox activity or ROS generation. © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e100 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.MetricsAuthor Information Jung-Sik Huh Aurora, CO More articles by this author Fernando J. Kim Aurora, CO More articles by this author Hyeon Ju Kim Aurora, CO More articles by this author Hari Koul Aurora, CO More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...