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 micromol/l) 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 micromol/l 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 micromol/l), 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 micromol/l.