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: 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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Authors | Xiu-Xian Wu, Yoshiyuki Kakehi, Xing-Hua Jin, Masashi Inui, Mikio Sugimoto |
Journal | Urology
(Urology)
Vol. 73
Issue 1
Pg. 193-9
(Jan 2009)
ISSN: 1527-9995 [Electronic] United States |
PMID | 18692875
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Vitamins
- Caspases
- Tocopherols
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Topics |
- Apoptosis
(drug effects)
- Carcinoma, Renal Cell
(drug therapy, enzymology, pathology)
- Caspases
(physiology)
- Drug Screening Assays, Antitumor
- Humans
- Kidney Neoplasms
(drug therapy, enzymology, pathology)
- Tocopherols
(therapeutic use)
- Tumor Cells, Cultured
- Vitamins
(therapeutic use)
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