Lycopene-induced growth inhibition of androgen-independent human prostate cancer cells in vitro via PPARγ-LXRα-ABCA1 pathway

• Main Authors: Ya-Ling Lu, 呂雅苓
• Other Authors: 胡淼琳
• Format: Others
• Language: zh-TW
• Published: 2008
• Online Access: http://ndltd.ncl.edu.tw/handle/18007455121772647153

碩士 === 國立中興大學 === 食品暨應用生物科技學系 === 96 === Carotenoids including lycopene and β-carotene possess several common biological functions such as photoprotection, antioxidant effects, and immunomodulatory and anticancer activity. Studies have suggested that higher intakes of lycopene are associated with a reduced risk of several types of cancer, such as prostate cancer, hepatoma and coronary heart disease. Although lycopene has been shown to inhibit proliferation, its mechanism of action is poorly understood. Here, we used androgen-independent human prostate cancer cells to test whether lycopene can inhibit the growth of prostate cancer via up-regulation of the expression of liver X receptor-target gene. The antiproliferative activity of lycopene may be due to LXR signaling. Androgen-independent human prostate cancer cells (DU145、PC-3) were incubated with different concentration of lycopene (2.5, 5, 10, 20μM), and the free cholesterol in medium increased but total intracellular cholesterol decreased. At the same time, the expression of PPARγ, LXRα, ABCA1 was enhanced in a dose-dependent manner from 2.5μM to 10μM. The treatment of prostate cancer cells with 10μM lycopene for 12, 24 and 48 h promoted cellular cholesterol efflux in a time-dependent manner from 12 h to 24 h, meanwhile expression of PPARγ, LXRα, ABCA1 was also raised respectively. Addition of different specific antagonists of PPARγ(GW9662),LXRα (GGPP) to prostate cancer cells significantly suppressed lycopene-induced cholesterol efflux. In addition treatment with specific inhibitors of PPARγ orLXRα decreased lycopene-induced ABCA1 mRNA and protein expression. The present results indicate that lycopene promotes cholesterol efflux from Androgen-independent human prostate cancer cells, and the underlying mechanism of this action is PPARγ-LXRα-ABCA1 dependent pathway. These results suggest that the effect of lycopene on proliferation may be mediated through the liver X recetor signaling pathway.