Combination therapy with vitamins C plus E inhibits survivin and human prostate cancer cell growth.

Combination therapy with vitamins C plus E inhibits survivin and human prostate cancer cell growth.

Gunawardena K, Campbell LD, Meikle AW.

Departments of Internal Medicine and Pathology, ARUP Institute, University of Utah, Salt Lake City, Utah 84108, USA.

BACKGROUND: We postulated that combinations of C and E vitamins modulate the antioxidant network and blocks survivin gene expression in androgen-responsive and non-responsive human prostate cancer cell (HPCC) lines. METHODS: ALVA-101 and DU-145 cell growth and apoptosis were estimated using the Cell Titer 96 AQ and cell death detection ELISA. Reverse transcription-polymerase chain reaction, Western blot and electrophoretic mobility shift assay were used to quantify survivin mRNA, protein, nuclear factor kappa B (NF-kappaB), and activator protein-1 (AP-1). RESULTS: All the tested combinations of vitamins C and E (25-100 microM, 72 hr) reduced cell growth (4-83%). Vitamin C enhanced the growth suppressive effect of vitamin E. Apoptosis was enhanced (25-45%) (vitamins = 100 microM, 24 hr). Survivin mRNA was decreased (26-29%) (vitamins = 250 microM, 24 hr), and survivin protein was decreased (>90%) (vitamins = 100 microM, 72 hr). NF-kappaB and AP-1 activities were increased (vitamins = 100 microM, 24 hr). CONCLUSIONS: The combinations of vitamins C and E are potent inducers of apoptosis in HPCC and suppressers of surviving, an antiapoptotic factor. Copyright 2004 Wiley-Liss, Inc.

PMID: 15042608 [PubMed - indexed for MEDLINE]
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