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Vitamin E succinate induced apoptosis and enhanced chemosensitivity to paclitaxel in human bladder cancer cells in vitro and in vivo


To whom correspondence should be addressed. E-mail: eiji-k@kb3.so-net.ne.jp


There have been several studies on the antitumor activities of vitamin E succinate (α-TOS) as complementary and alternative medicine. In the present study, we investigated the cytotoxic effect of α-TOS and the enhancement of chemosensitivity to paclitaxel by α-TOS in bladder cancer. KU-19-19 and 5637 bladder cancer cell lines were cultured in α-TOS and/or paclitaxel in vitro. Cell viability, flow cytometric analysis, and nuclear factor-kappa B (NF-κB) activity were analyzed. For in vivo therapeutic experiments, pre-established KU-19-19 tumors were treated with α-TOS and/or paclitaxel. In KU-19-19 and 5637 cells, the combination treatment resulted in a significantly higher level of growth inhibition, and apoptosis was significantly induced by the combination treatment. NF-κB was activated by paclitaxel; however, the activation of NF-κB was inhibited by α-TOS. Also, the combination treatment significantly inhibited tumor growth in mice. In the immunostaining of the tumors, apoptosis was induced and proliferation was inhibited by the combination treatment. Combination treatment of α-TOS and paclitaxel showed promising anticancer effects in terms of inhibiting bladder cancer cell growth and viability in vitro and in vivo. One of the potential mechanisms by which the combination therapy has synergistic cytotoxic effects against bladder cancer may be that α-TOS inhibits NF-κB induced by chemotherapeutic agents. (Cancer Sci 2009;)