Positive Health Online

Abstract

GUNAWARDENA, MURRAY and MEIKLE, Department of Medicine, University of Utah School of Medicine, Salt Lake City 84132, USA investigated whether vitamin E and other antioxidants inhibit human prostate cancer cells through apoptosis.

Background

Many human prostate cancer cells have escaped the apoptotic effects of natural regulators of cell growth such as transforming growth factor beta l (TGF beta-1) and tumor necrosis factor (TNF).

Methodology

DU-145 (androgen-unresponsive), LNCaP (androgen-responsive), and ALVA-101 (androgen moderately responsive) prostate cancer cells were grown in RPMI-1640 medium supplemented with bovine foetal calf serum and antibiotics, and were treated with various antioxidants for 1-7 days. Cell growth was then determined with the Cell Titre 96 AQ assay, and apoptosis was assessed by cell death detection ELISA, nuclear morphology, and TUNEL techniques.

Results

Cells treated with or without alpha-tocopherol (vitamin E) for 1-7 days at concentrations from 0.078-2.5 g/ml resulted in modestly affected cell growth compared to other antioxidants tested. Tocopherol produced a significant growth inhibition of ALVA-101 and LNCaP cells. DU-145 cells were not growth-inhibited significantly. However, pyrrolidinedithiocarbamate (PDTC) produced a significant inhibition of DU-145 and ALVA-101 cells. A significant and maximum inhibition of LNCaP cells occurred at all concentrations of PDTC (2. 5-20 g/ml). A third compound, diethyldithiocarbamic acid (DETC), incubated for 1-7 days, produced a significant dose response suppression of cell growth of DU-145 and ALVA-101 cells. LNCaP cells were inhibited by DETC. All three antioxidants tested stimulated apoptosis in actively dividing ALVA-101, DU-145, and LNCaP cells, but confluent cells were affected less. Testosterone had additive inhibitory effects when combined with PDTC in ALVA-101 cells; however, the other cell lines were not influenced.

Conclusion

These results demonstrate that antioxidants modulate human prostate cancer cell proliferation by altering apoptosis in dividing cells, and this necrosis or apoptosis in confluent cells is not as effective.

References

Gunawardena K et al. Vitamin E and other antioxidants inhibit human prostate cancer cells through apoptosis. Prostate 44(4): 287-95. Sep 2000.

Comment

It is encouraging to see that so much molecularly focussed research is being performed to elucidate and understand the mechanisms behind the anti-cancer properties of nutrients such as isoflavones, essential fatty acids and antioxidants.