Liarozole amplifies retinoid-induced apoptosis in human prostate cancer cells.
Beta-carotene, canthaxanthin and retinoic acid (RA) inhibited growth of human DU145 prostate cancer cells by 45, 56 and 18%, respectively. Lycopene was also found to inhibit cell growth. Other carotenoids including xanthophyll (lutein), cryptoxanthin and zeaxanthin were less effective. Liarozole (a novel imidazole-derived inhibitor of intracellular RA catabolism) had a modest effect upon cell growth, this drug significantly amplified the pro-apoptotic actions of beta-carotene and RA. RA-induced expression of thymosin beta-10, an apoptotic accelerant, was associated with increased nuclear DNA nicking as measured using TUNEL. Liarozole enhanced the proapoptotic actions of RA upon DNA fragmentation in a dose-dependent manner. These actions were accompanied by inhibition of the cell survival factor bcl-2. Liarozole may thus prove useful as a novel chemotherapeutic/chemopreventive agent by boosting retinoid-induced apoptosis in the prostate.
Hall
A K
AK
Department of Pharmacology, University of Cambridge, UK.
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015152:Blotting, Northern; D002455:Cell Division; D053938:DNA Fragmentation; D004357:Drug Synergism; D019254:Genes, bcl-2 / Q000187:drug effects; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D008297:Male; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000235:genetics; D012333:RNA, Messenger; D012176:Retinoids / Q000494:pharmacology*; D013947:Thymosin / Q000235:genetics; D014212:Tretinoin / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects; D019207:beta Carotene / Q000494:pharmacology
D000970:Antineoplastic Agents; D007093:Imidazoles; D012333:RNA, Messenger; D012176:Retinoids; D019207:beta Carotene; D014212:Tretinoin; D013947:Thymosin; C061121:liarozole