Effect of permixon on human prostate cell growth: Lack of apoptotic action

Abstract

Permixon, a phytotherapeutic agent derived from the saw palmetto or Serenoa repens plant, is a lipid/sterol extract that is believed to interfere with 5alpha-reductase activity, thus inhibiting prostate growth. In this study, we investigated the magnitude and specificity of the effect of Permixon on cell proliferation and apoptosis in human prostate cancer cells. The effect of Permixon was examined in androgen-independent PC-3 prostate cancer cells, androgen-sensitive LNCaP prostate cancer cells, and MCF-7 breast cancer cells in vitro. Cell growth, apoptosis induction, and cell proliferation was studied after exposure to Permixon at two concentrations (10 and 100 microg/ml). Cell proliferation and cell cycle progression were determined after 24 hr on the basis of (3)[H]-thymidine incorporation assay and flowcytometric analysis, respectively. Apoptosis induction was evaluated in treated and untreated cultures using the Hoescht staining and caspase-3 activation. Exposure of prostate and breast cancer cells to a high dose of Permixon (100 microg/ml) resulted in a significant decrease in the rate of cell growth; an effect that was not time-dependent and was not associated with cell cycle arrest. Permixon treatment (at either high or low dose) had no effect on apoptosis induction in prostate cancer cell lines (P > 0.6). Furthermore, in vitro Permixon was a weak inhibitor of 5alpha-reductase activity type 2 in prostatic homogenates. The results indicate the ability of Permixon to affect prostate cancer cell growth without inducing apoptosis or cell cycle arrest. This effect was not prostate-specific and was only manifested at high concentrations of Permixon. Furthermore our findings indicate that Permixon is weak inhibitor of 5alpha-reductase compared to finasteride. This study challenges previous evidence on the anti-growth effect of Permixon in the prostate and its ability to inhibit 5alpha-reductase activity, while questioning apoptosis as a mechanism of action of this phytotherapeutic against prostate growth, a concept that may have therapeutic significance.