Please use this identifier to cite or link to this item: http://hdl.handle.net/11455/51094
標題: Lycopene-induced growth inhibition of androgen-independent human prostate cancer cells in vitro via PPARγ-LXRα-ABCA1 pathway
茄紅素可促進PPARγ-LXRα-ABCA1之途徑而抑制 男性荷爾蒙非依賴型前列腺癌細胞之生長
作者: Lu, Ya-Ling
呂雅苓
關鍵字: 茄紅素;Lycopene;PPAR;LXR;ABCA1;前列腺癌細胞;膽固醇運輸;PPAR;LXR;ABCA1;prostate cancer;cholesterol efflux
出版社: 食品暨應用生物科技學系
摘要: 
類胡蘿蔔素(Carotenoids),包含茄紅素(lycopene)與β-胡蘿蔔素(β-carotene),在生理上具有許多重要功能,包括:光保護作用(photoprotection)、抗氧化作用、免疫調節作用(immunomodulatory)以及抗癌活性(anti-cancer)。許多研究指出攝取富含茄紅素的食物可以降低多種癌症的發生率,如前列腺癌、肺癌等。然而茄紅素在抑制前列腺癌生長的機制目前尚未明確。因此本研究目標即在探討茄紅素在抑制前列腺癌生長中所扮演的調控角色與機制為何。本研究提出一假說,亦即:茄紅素可促進peroxisome proliferator-activated receptor gamma (PPARγ)和liver X receptor alpha (LXRα)之途徑,繼而增加下游基因ATP-binding cassette transporter A1(ABCA1)的表現,而提高細胞內膽固醇之輸出,進而抑制男性荷爾蒙非依賴型前列腺癌細胞的生長。
本研究以茄紅素不同濃度(2.5、5、10、20 μM)分別處理男性荷爾蒙非依賴型前列腺癌細胞(DU145、PC-3)。結果顯示,茄紅素會造成細胞內的膽固醇量減少,而medium中的游離膽固醇量增加,且PPARγ、LXRα和ABCA1的表現量隨著茄紅素的濃度增加(2.5 μM至10 μM)而增加,呈濃度效應。以10 μM茄紅素與DU145細胞培養12、24及48小時,隨著時間增加(12小時到24小時),膽固醇運輸量增加;同時PPARγ、LXRα和ABCA1的表現量也跟著上升。以前列腺癌細胞分別處理PPARγ(GW9662)、LXRα(GGPP)專一性的拮抗劑時,會顯著阻礙茄紅素誘導的膽固醇運輸,也降低了ABCA1的蛋白質和mRNA表現量。
總合以上結果,我們證實了茄紅素可藉由PPARγ- LXRα-ABCA1路徑促進膽固醇運輸,而抑制男性荷爾蒙非依賴型前列腺癌細胞的生長。因此,本研究結果可提供茄紅素在預防和治療前列腺癌的新理論觀念。

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.
URI: http://hdl.handle.net/11455/51094
Appears in Collections:食品暨應用生物科技學系

Show full item record
 

Google ScholarTM

Check


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.