Vitamin E and other antioxidants inhibit human prostate cancer cells through apoptosis

BACKGROUND. Many human prostate cancer cells have escaped the apoptotic eff ects of natural regulators of cell growth such as transforming growth facto r beta 1 (TCF beta-1) and tumor necrosis factor (TNF). METHODS. Prostate cancer cell growth was investigated by treating with anti oxidants. DU-145 (androgen-unresponsive), LNCaP (androgen-responsive), and ALVA-101 (androgen moderately responsive) were grown in RPMI-1640 medium su pplemented with bovine fetal calf serum and antibiotics, and were treated w ith various antioxidants for 1-7 days. Cell growth was then determined with the Cell Titer 96 AQ assay, and apoptosis was assessed by cell death detec tion ELISA, nuclear morphology, and TUNEL techniques. RESULTS. Cells treated with or without (+/-)-alpha-tocopherol (vitamin E) f or 1-7 days at concentrations from 0.078-2.5 mu g/ml modestly affected cell growth compared to other antioxidants tested. Tocopherol produced a signif icant (P < 0.01) inhibition of ALVA-101 and LNCaP (10-24% of control; 0.078 -2.5 mu g/ml; at 6 days; n = 6). DU-145 cells were not growth-inhibited sig nificantly. However, pyrrolidinedithiocarbamate (PDTC) produced a significa nt (P < 0.01, n = 6; 17-80% of control; 2.5-20 mu g/ml; 1-7 days) inhibitio n of DU-145 and ALVA-101 cells. A significant (P < 0.01) and maximum inhibi tion of LNCaP cells occurred at all concentration of PDTC (2.5-20 mu g/ml). A third compound, diethyldithiocarbamic acid (DETC), incubated for 1-7 day s, produced a significant dose response suppression of cell growth of DU-14 5 and ALVA-101 cells (P < 0.01; 14-88% of control; 1.25-80 mu g/ml; n = 6). LNCaP cells were inhibited by DETC (P < 0.01; 28% of control; 1.25-80 mu g /ml; n = 6). All three antioxidants tested stimulated apoptosis in actively dividing ALVA-101, DU-145, and LNCaP cells (P < 0.01; n = 6), but confluen t cells were affected less. Testosterone had additive inhibitory effects wh en combined with PDTC in ALVA-101 cells; however, the other cell lines were not influenced. CONCLUSIONS. These results demonstrate that antioxidants modulate human pro state cancer cell proliferation by altering apoptosis in dividing cells, an d this necrosis or apoptosis in confluent cells is not as effective. (C) 20 00 Wiley-Liss, Inc.