LIAROZOLE AMPLIFIES RETINOID-INDUCED APOPTOSIS IN HUMAN PROSTATE-CANCER CELLS

Beta-carotene, canthaxanthin and retinoic acid (RA) inhibited growth o f human DU145 prostate cancer cells by 45, 56 and 18%, respectively. L ycopene was also found to inhibit cell growth. Other carotenoids inclu ding xanthophyll (lutein), cryptoxanthin and zeaxanthin were less effe ctive. Liarozole (a novel imidazole-derived inhibitor of intracellular RA catabolism) had a modest effect upon cell growth, this drug signif icantly amplified the pro-apoptotic actions of beta-carotene and RA. R A-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 fragmenta tion in a dose-dependent manner. These actions were accompanied by inh ibition of the cell survival factor bcl-2. Liarozole may thus prove us eful as a novel chemotherapeutic/chemopreventative agent by boosting r etinoid-induced apoptosis in the prostate.