Pannarin inhibits cell growth and induces cell death in human prostate carcinoma DU-145 cells

In the course of our continuing search for new natural anticancer compounds for treatment and/or prevention of prostate cancer, our laboratory has focused its search on poorly investigated lichen metabolites, sphaerophorin, pannarin and epiphorellic acid-1. To this end, we treated DU-145, a cell line resembling the last stage of prostate carcinoma, with different concentrations (6-50 mu mol/I) of these compounds for 72 h. Our data clearly evidenced that these lichen metabolites inhibit the growth of human prostate carcinoma DU-145 cells, but pannarin exhibits a higher effect. Our data show an induction of apoptotic death of advanced prostate cancer cells by sphaerophorin, pannarin and epiphorellic acid-1. In fact, a significant (P < 0.001) increase in caspase-3 enzyme activity occurred in DU-145 cells treated with all lichen compounds at 12 and 25 mu mol/I concentrations, correlated to a high DNA fragmentation, but without the disruption of the plasma membrane, as evaluated by the percentage of lactic dehydrogenase release. Alternatively, we found a low, but significant (P < 0.01) lactic dehydrogenase release at higher concentrations (50 mu mol/I), suggesting that in these experimental conditions sphaerophorin, pannarin and epiphorellic acid-1 induce necrosis in DU-145 cells, through the increase in reactive oxygen species. generation. The experimental evidence is further confirmed by caspase-3 activity results, evidencing a reduction in the activity of this protease at a higher concentration, 50 mu mol/I. Anti-Cancer Drugs 17:1163-1169 (c) 2006 Lippincott Williams & Wilkins.