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Liarozole amplifies retinoid-induced apoptosis in human prostate cancer cells
1Department of Pharmacology, University of Cambridge, UK.
Abstract:
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.
Insights
Beta-carotene and canthaxanthin significantly inhibit prostate cancer cell growth. Liarozole, an RA catabolism inhibitor, enhances retinoid-induced apoptosis, suggesting potential as a chemopreventive agent.
Area of Science:
- Oncology
- Molecular Biology
- Nutritional Science
Background:
- Prostate cancer remains a significant health concern.
- Carotenoids and retinoids are investigated for their potential anti-cancer properties.
- Understanding mechanisms of action is crucial for developing effective therapies.
Purpose of the Study:
- To evaluate the effects of various carotenoids and retinoic acid (RA) on DU145 prostate cancer cell growth.
- To investigate the synergistic effects of liarozole, an RA metabolism inhibitor, with beta-carotene and RA.
- To elucidate the molecular mechanisms underlying retinoid-induced apoptosis in prostate cancer cells.
Main Methods:
- Cell viability assays were performed on DU145 prostate cancer cells.
- Treatment groups included beta-carotene, canthaxanthin, lycopene, other carotenoids, retinoic acid (RA), and liarozole.
- Apoptosis was assessed by measuring DNA fragmentation (TUNEL assay) and expression of apoptosis-related genes (thymosin beta-10, bcl-2).
Main Results:
- Beta-carotene, canthaxanthin, and RA inhibited DU145 cell growth by 45%, 56%, and 18%, respectively.
- Lycopene also inhibited cell growth, while other carotenoids showed lesser effects.
- Liarozole significantly amplified the pro-apoptotic effects of beta-carotene and RA, increasing DNA fragmentation and downregulating bcl-2.
Conclusions:
- Specific carotenoids and retinoic acid demonstrate significant anti-proliferative effects on prostate cancer cells.
- Liarozole potentiates retinoid-induced apoptosis, offering a potential strategy for prostate cancer chemoprevention.
- Targeting RA metabolism with agents like liarozole may enhance the efficacy of retinoid-based cancer therapies.