title: Lycopene inhibits the proliferation of androgen-dependent human prostate tumor cells through activation of PPARγ-LXRα-ABCA1 pathway.
abstract: The activation of nuclear receptors, peroxisome proliferator-activated receptor gamma (PPARγ) and liver X receptor alpha (LXRα), has been shown to inhibit the growth of prostate cancer cells. This study examined whether the anti-proliferative effect of lycopene on androgen-dependent human prostate cancer (LNCaP) cells involves the up-regulation of the expression of PPARγ and LXRα. As expected, lycopene treatment (2.5-10 μM) significantly inhibited the proliferation of LNCaP cells during incubation for 96 h. Lycopene significantly increased the protein and mRNA expression of PPARγ and LXRα at 24 and 48 h, while the increased in the expression of ATP-binding cassette transporter 1 (ABCA1) was only evident 96 h. In addition, lycopene significantly decreased cellular total cholesterol levels and increased apoA1 protein expression at 96 h. Incubation of LNCaP cells with lycopene (10 μM) in the presence (20 μM) of a specific antagonist of PPARγ (GW9662) and LXRα (GGPP) restored the proliferation of LNCaP cells to the control levels and significantly suppressed protein expression of PPARγ and LXRα as well as increased cellular total cholesterol levels. LXRα knockdown by siRNA against LXRα significantly enhanced the proliferation of LNCaP cells, whereas si-LXRα knockdown followed by incubation with lycopene (10 μM) restored the proliferation to the control level. The present study is the first to demonstrate that the anti-proliferative effect of lycopene on LNCaP cells involves the activation of the PPARγ-LXRα-ABCA1 pathway, leading to reduced cellular total cholesterol levels.
authors.affiliation: Department of Food Science and Biotechnology, National Chung Hsing University, Taichung, Taiwan 402, ROC.
authors.forename: Chih-Min
authors.initials: CM
authors.lastname: Yang
authors.forename: I-Hsuan
authors.initials: IH
authors.lastname: Lu
authors.forename: Huei-Yan
authors.initials: HY
authors.lastname: Chen
authors.forename: Miao-Lin
authors.initials: ML
authors.lastname: Hu
mesh_terms: D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism*; D000728:Androgens / Q000378:metabolism; D000813:Anilides / Q000494:pharmacology; D016632:Apolipoprotein A-I / Q000235:genetics / Q000378:metabolism; D002338:Carotenoids / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002784:Cholesterol / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D000071518:Liver X Receptors; D000077276:Lycopene; D008297:Male; D053858:Metabolic Networks and Pathways; D057093:Orphan Nuclear Receptors / Q000235:genetics / Q000378:metabolism*; D047495:PPAR gamma / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D034741:RNA, Small Interfering; D015854:Up-Regulation
chemical_list: C457499:2-chloro-5-nitrobenzanilide; C577836:ABCA1 protein, human; C505693:APOA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D000728:Androgens; D000813:Anilides; D016632:Apolipoprotein A-I; D000071518:Liver X Receptors; C000605213:NR1H3 protein, human; D057093:Orphan Nuclear Receptors; D047495:PPAR gamma; D034741:RNA, Small Interfering; D002338:Carotenoids; D002784:Cholesterol; D000077276:Lycopene