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• W2068348043 abstract "You have accessJournal of UrologyBladder Cancer: Basic Research II1 Apr 2010980 VITAMIN E DERIVATIVES IN COMBINATION WITH ANTICANCER DRUGS FOR BLADDER CANCER CELLS: NF-κB IS A KEY MOLECULE FOR THE SYNERGISTIC EFFECTS OF α-TOCOPHEROL SUCCINATE AND PACLITAXEL Kunimitsu Kanai, Eiji Kikuchi, Shuji Mikami, Eriko Suzuki, Akira Miyajima, and Mototsugu Oya Kunimitsu KanaiKunimitsu Kanai More articles by this author , Eiji KikuchiEiji Kikuchi More articles by this author , Shuji MikamiShuji Mikami More articles by this author , Eriko SuzukiEriko Suzuki More articles by this author , Akira MiyajimaAkira Miyajima More articles by this author , and Mototsugu OyaMototsugu Oya More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2010.02.1927AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Vitamin E has an antioxidant effect and is an essential fatty acid naturally occurring as 4 (α-, β-, γ-, and δ-) tocopherols and 4 tocotrienols. The present study was performed to investigate the cytotoxic effect of vitamin E derivatives and the enhancement of chemosensitivity to anticancer drugs by vitamin E derivatives in the treatment of bladder cancer. METHODS KU-19-19 and 5637 bladder cancer cell lines were cultured in vitro in vitamin E derivatives (α-tocopherol [α-TOH], α-tocopherol acetate [α-TOA], α-tocopherol succinate [α-TOS], and γ-tocotrienol [γ-T3]) and/or anticancer drugs (cisplatin, gemcitabine, and paclitaxel). Cell viability, flow cytometric analysis, the nuclear factor-kappa B (NF-κB) activity, and the NF-κB pathway were analyzed. For in vivo therapeutic experiments, pre-established KU-19-19 tumors were treated with drugs proved to have the most synergistic effects in vitro. RESULTS α-TOS and γ-T3 significantly inhibited cell proliferation in a time- and dose-dependent manner in KU-19-19 and 5637 cells. Meanwhile, α-TOH and α-TOA did not exhibit any cytotoxic effects. In the combination treatment, α-TOS combined with paclitaxel had the most synergistic effects in both KU-19-19 and 5637 cells. The combination index values of α-TOS and paclitaxel in KU-19-19 and 5637 cells were 0.87 ± 0.17 and 0.64 ± 0.23, respectively (p<0.05). NF-κB was activated by paclitaxel; however, the activation of NF-κB was inhibited by α-TOS. α-TOS co-administered with paclitaxel enhances cell apoptosis through down-regulation of pro-survival proteins (phospho-IκBα) and anti-apoptotic proteins (c-IAP1). Also, the combination treatment significantly inhibited tumor growth in mice. α-TOS, paclitaxel and the combination treatment significantly suppressed tumor growth to 61%, 63%, and 33%, respectively, of the tumor volume in the control group on the 28th day from implantation (p<0.05). Immunostaining assay of the tumors revealed that apoptosis was induced and proliferation was inhibited by the combination treatment. CONCLUSIONS Our results demonstrate the efficacy and therapeutic potential of α-TOS and its enhancement of chemosensitivity to paclitaxel in bladder cancer cells. Tokyo, Japan© 2010 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 183Issue 4SApril 2010Page: e381 Advertisement Copyright & Permissions© 2010 by American Urological Association Education and Research, Inc.MetricsAuthor Information Kunimitsu Kanai More articles by this author Eiji Kikuchi More articles by this author Shuji Mikami More articles by this author Eriko Suzuki More articles by this author Akira Miyajima More articles by this author Mototsugu Oya More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ..." @default.
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• W2068348043 title "980 VITAMIN E DERIVATIVES IN COMBINATION WITH ANTICANCER DRUGS FOR BLADDER CANCER CELLS: NF-κB IS A KEY MOLECULE FOR THE SYNERGISTIC EFFECTS OF α-TOCOPHEROL SUCCINATE AND PACLITAXEL" @default.
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