Published in Cancer Detection and Prevention 2002; 26(2).

Testosterone is a potential augmentor of antioxidant induced apoptosis in human prostate cancer cells

Kushlani Gunawardena PhD, Darrell K. Murray PhD, A. Wayne Meikle MD

Division of Endocrinology, Departments of Internal Medicine and Pathology, ARUP Institute, University of Utah, Room 4Cl16, 50 North Medical Drive, Salt Lake City, UT 84132, USA

Accepted 12 February 2002

We have investigated the effect of antioxidant-induced apoptosis in human prostate cancer cell lines that is augmented by testosterone (T). In this study, DU-145 (androgen unresponsive), ALVA-101 (partially androgen responsive), and LNCaP (androgen responsive) were grown in tissue culture with RPMII640 medium, 5-10% fetal bovine serum (FBS), antibiotics and 5% CO2. Treatment with 2.5-20 µg/ml of PDTC significantly (P < 0.05, n = 6) lowered cell growth in all three cells 2-60% following treatment for 1-7 days. T (10-12 M) alone enhances cell growth in androgen responsive cells. In contrast, the combination of PDTC and T significantly (P < 0.05, n = 6) augmented the PDTC induction of apoptosis in the androgen responsive cells, (ALVA-101 and LNCaP), but not in the androgen unresponsive cells (DU-145). PDTC reduced the nuclear NF-κB, as determined with an electrophoretic mobility shift assay (EMSA), to 50% of the control in LNCaP cells, 65% in ALVA-101 cells and 45% in DU-145 cells, but the combination of PDTC and T was not more potent than PDTC alone in any of the cell lines. PDTC suppressed both the AR mRNA and protein expression and reversed the stimulatory effect of T on androgen receptor (AR) protein synthesis in LNCaP and AVLA-101 cells. In conclusion, PDTC is a potent growth inhibitor and an inducer of apoptosis in human prostate cancer cells by reducing nuclear NF-κB and AR protein expression. PDTCs suppression of AR synthesis and nuclear NF-κB in response to T may contribute to its enhancement of apoptosis observed with T and PDTC compared to PDTC alone.

KEY WORDS: Prostate cancer, ALVA-IOl, LNCaP, Anlioxidants, Testosterone, Apoptosis, .