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

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.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).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).The combinations of vitamins C and E are potent inducers of apoptosis in HPCC and suppressers of surviving, an antiapoptotic factor.