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Combination therapy with vitamins C plus E inhibits survivin and human prostate cancer cell growth
Author(s) -
Gunawardena Kushlani,
Campbell L. David,
Meikle A. Wayne
Publication year - 2004
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.20018
Subject(s) - survivin , apoptosis , cell growth , programmed cell death , prostate cancer , biology , endocrinology , medicine , microbiology and biotechnology , cancer , biochemistry
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‐κB), and activator protein‐1 (AP‐1). RESULTS All the tested combinations of vitamins C and E (25–100 μM, 72 hr) reduced cell growth (4–83%). Vitamin C enhanced the growth suppressive effect of vitamin E. Apoptosis was enhanced (25–45%) (vitamins = 100 μM, 24 hr). Survivin mRNA was decreased (26–29%) (vitamins = 250 μM, 24 hr), and survivin protein was decreased (>90%) (vitamins = 100 μM, 72 hr). NF‐κB and AP‐1 activities were increased (vitamins = 100 μM, 24 hr). CONCLUSIONS The combinations of vitamins C and E are potent inducers of apoptosis in HPCC and suppressers of surviving, an antiapoptotic factor. © 2004 Wiley‐Liss, Inc.