Antiandrogen-like actions of an antioxidant on survivin, Bcl-2 and PSA in human prostate cancer cells

Background: Androgens, while essential for prostate gland development, have been postulated to contribute to carcinogenesis, and antioxidants have been postulated to suppress prostate cancer development. We theorized that antioxidants might suppress prostate cancer cell growth by blocking androgen effects on cell survival. This hypothesis was tested by in vitro studies conducted in ALVA-101, an androgen responsive human prostate cancer cell line. Methods: ALVA-101 was cultured with or without testosterone (T, 10(-12) M) and pyrrolidinedithiocarbamate (PDTC, 10 mu g/mL). Cell Titer 96 AQ, electrophoretic mobility shift assay (EMSA), reverse transcription-polymerase chain reaction (RT-PCR), Northern and Western blot were used to quantify the cell growth, nuclear factor-kappa B (NF-kappa B) activity, mRNAs of survivin, Bcl-2, androgen receptor (AR) and prostate specific antigen (PSA), and proteins of AR and survivin. Results: PDTC suppressed EMSA of NF-kappa B and significantly decreased (p < 0.05) T's stimulatory effects on cell growth, mRNAs of survivin, Bcl-2, AR and PSA and synthesis of proteins of AR and survivin. Antisense to both survivin and Bcl-2 suppressed cell growth. Conclusions: PDTC, a potent inducer of apoptosis, exerts antiandrogen-like action by reducing AR protein and reversing the stimulatory effects of androgen on potent inhibitors of apoptosis. (c) 2005 International Society for Preventive Oncology. Published by Elsevier Ltd. All rights reserved.