Combination Treatment of Renal Cell Carcinoma with Belinostat and 5-Fluorouracil: A Role for Oxidative Stress Induced DNA Damage and HSP90 Regulated Thymidine Synthase

No AccessJournal of UrologyInvestigative Urology1 May 2015Combination Treatment of Renal Cell Carcinoma with Belinostat and 5-Fluorouracil: A Role for Oxidative Stress Induced DNA Damage and HSP90 Regulated Thymidine Synthase Mi Joung Kim, Jee Suk Lee, Sang Eun Park, Hye-Jin Yi, In Gab Jeong, Jong Soon Kang, Jieun Yun, Joo-Yong Lee, Seonggu Ro, Jung Shin Lee, Eun Kyung Choi, Jung Jin Hwang, and Choung-Soo Kim Mi Joung KimMi Joung Kim Institute for Innovative Cancer Research, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea , Jee Suk LeeJee Suk Lee Institute for Innovative Cancer Research, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea , Sang Eun ParkSang Eun Park Institute for Innovative Cancer Research, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea Department of Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea , Hye-Jin YiHye-Jin Yi Institute for Innovative Cancer Research, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea , In Gab JeongIn Gab Jeong Institute for Innovative Cancer Research, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea Department of Urology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea , Jong Soon KangJong Soon Kang Bio-Evaluation Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea , Jieun YunJieun Yun Bio-Evaluation Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea , Joo-Yong LeeJoo-Yong Lee Department of Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea , Seonggu RoSeonggu Ro CrystalGenomics, Inc., Gyeonggi-Do, Republic of Korea , Jung Shin LeeJung Shin Lee Institute for Innovative Cancer Research, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea , Eun Kyung ChoiEun Kyung Choi Institute for Innovative Cancer Research, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea Department of Radiation Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea Center for Development and Commercialization of Anti-Cancer Therapeutics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea , Jung Jin HwangJung Jin Hwang Institute for Innovative Cancer Research, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea Department of Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea , and Choung-Soo KimChoung-Soo Kim Institute for Innovative Cancer Research, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea Department of Urology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea View All Author Informationhttps://doi.org/10.1016/j.juro.2014.11.091AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: Despite several therapeutic options renal cell carcinoma is associated with a poor clinical outcome. Therefore, we investigated whether combining 5-fluorouracil with the histone deacetylase inhibitor belinostat would exert a synergistic effect on renal cell carcinoma cells in vitro and in vivo. Materials and Methods: We used SN12C cells treated with 5-fluorouracil and/or belinostat in vitro and in xenograft experiments in vivo. Cell viability and death mechanisms were assessed by MTS assay and Western blot. To investigate the role of reactive oxygen species we used H2DCF-DA, reactive oxygen species scavengers and the roGFP2 construct. Results: Belinostat potentiated the anticancer effect of 5-fluorouracil. It synergistically induced apoptosis by activating caspases and increasing the subG1 cell population. Effects on reactive oxygen species mediated DNA damage included decreased thioredoxin expression and increased levels of TBP-2, γ-H2AX and Ac-H3. Furthermore, belinostat attenuated the 5-fluorouracil mediated induction of thymidylate synthase via HSP90 hyperacetylation. 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Google Scholar © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 5May 2015Page: 1660-1668Supplementary Materials Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.Keywordsbelinostatcarcinomakidneyrenal celldrug therapyfluorouracilcombinationMetricsAuthor Information Mi Joung Kim Institute for Innovative Cancer Research, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea More articles by this author Jee Suk Lee Institute for Innovative Cancer Research, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea More articles by this author Sang Eun Park Institute for Innovative Cancer Research, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea Department of Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea More articles by this author Hye-Jin Yi Institute for Innovative Cancer Research, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea More articles by this author In Gab Jeong Institute for Innovative Cancer Research, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea Department of Urology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea More articles by this author Jong Soon Kang Bio-Evaluation Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea More articles by this author Jieun Yun Bio-Evaluation Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea More articles by this author Joo-Yong Lee Department of Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea More articles by this author Seonggu Ro CrystalGenomics, Inc., Gyeonggi-Do, Republic of Korea Financial interest and/or other relationship with CrystalGenomics. More articles by this author Jung Shin Lee Institute for Innovative Cancer Research, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea More articles by this author Eun Kyung Choi Institute for Innovative Cancer Research, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea Department of Radiation Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea Center for Development and Commercialization of Anti-Cancer Therapeutics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea More articles by this author Jung Jin Hwang Institute for Innovative Cancer Research, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea Department of Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea More articles by this author Choung-Soo Kim Institute for Innovative Cancer Research, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea Department of Urology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea More articles by this author Expand All Advertisement PDF downloadLoading ...