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 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.
Russo
Alessandra
A
Department of Biological Chemistry, Medical Chemistry and Molecular Biology, University of Catania, V. le A. Doria 6, 95125, Catania, Italy. alrusso@unict.it
Piovano
Marisa
M
Lombardo
Laura
L
Vanella
Luca
L
Cardile
Venera
V
Garbarino
Juan
J
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001565:Benzoates / Q000494:pharmacology; D001584:Benzoxepins / Q000494:pharmacology*; D002277:Carcinoma / Q000378:metabolism / Q000473:pathology*; D053148:Caspase 3 / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D048708:Cell Growth Processes / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D053938:DNA Fragmentation / Q000187:drug effects; D053630:Depsides / Q000494:pharmacology*; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008011:Lichens / Q000737:chemistry; D008297:Male; D008954:Models, Biological; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D014407:Tumor Cells, Cultured
D000972:Antineoplastic Agents, Phytogenic; D001565:Benzoates; D001584:Benzoxepins; D053630:Depsides; D017382:Reactive Oxygen Species; C518877:epiphorellic acid-1; C518876:sphaerophorin; C085355:pannarin; D007770:L-Lactate Dehydrogenase; D053148:Caspase 3