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  • Title: Induction of apoptosis in human renal cell carcinoma cells by vitamin E succinate in caspase-independent manner.
    Author: Wu XX, Kakehi Y, Jin XH, Inui M, Sugimoto M.
    Journal: Urology; 2009 Jan; 73(1):193-9. PubMed ID: 18692875.
    Abstract:
    OBJECTIVES: Renal cell carcinoma (RCC) is one of the most drug-resistant malignancies, and an effective therapy is lacking for metastatic RCC. Vitamin E (VE) has been intensively studied as a chemopreventive agent for various cancer types. Preclinical investigations have suggested that VE succinate (VES) is the most effective analog of VE in cancer cells; however, no study of VES in RCC has been done. We investigated the anticancer activity of VES against RCC. METHODS: Cytotoxicity was assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Cell morphologic changes and cell viability were evaluated using phase-contrast microscopy and the trypan blue dye-exclusion test, respectively. Caspase activity was measured with a quantitative colorimetric assay. RESULTS: VES exerted dose- and time-dependent cytotoxicities against ACHN, a human RCC cell line, but VE and VE acetate did not. The cytotoxic effect was also observed in 2 other RCC cell lines, Caki-1 and Caki-2, and in primary RCC cells derived from 8 patients. Hoechst 33258 staining and DNA ladder analysis demonstrated that VES induced apoptosis in RCC cells. However, VES did not affect activation of caspase-3, -6, -8, or -9. Furthermore, inhibitors specific to caspase-8, -9, -6, and -3 did not block VES cytotoxicity and neither did the general caspase inhibitor VAD. CONCLUSIONS: VES might induce apoptosis and cytotoxicity against RCC cells in a caspase-independent manner and has potential in vivo applications in the treatment of drug-and/or immunotherapy-resistant RCC.
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