Induction of apoptosis in human renal cell carcinoma cells by vitamin E succinate in caspase-independent manner.

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.

• 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)

Chemical References

• Vitamins
• Caspases
• Tocopherols

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)