title: Lycopene and the LXRα agonist T0901317 synergistically inhibit the proliferation of androgen-independent prostate cancer cells via the PPARγ-LXRα-ABCA1 pathway.
abstract: In our previous study, we demonstrated that lycopene can inhibit the proliferation of androgen-dependent prostate LNCaP cancer cells through the activation of the peroxisome proliferator-activated receptor gamma (PPARγ)-liver X receptor alpha (LXRα)-ATP-binding cassette transporter 1 (ABCA1) pathway. However, it is still unclear whether lycopene possesses similar effects in androgen-independent prostate cancer cells DU145 and PC-3. As lycopene inhibited the proliferation of both cell types to a similar extent, we chose DU145 cells for most of the subsequent studies. We show that lycopene significantly increased protein and mRNA expression of PPARγ, LXRα and ABCA1 and cholesterol efflux (i.e., decreased cellular cholesterol and increased cholesterol in culture medium). Lycopene (10 μM) in the presence of a specific antagonist of PPARγ (GW9662) or of LXRα (GGPP) restored the proliferation of DU145 cells and significantly suppressed lycopene-induced protein and mRNA expression of PPARγ and LXRα and cholesterol efflux. Liver X receptor α knockdown by siRNA against LXRα significantly promoted the proliferation of DU145 cells, whereas si-LXRα knockdown followed by incubation with lycopene (10 μM) restored the proliferation to the control level. Furthermore, lycopene in combination with the LXRα agonist T0901317 exhibited synergistic effects on cell proliferation and protein expression of PPARγ, LXRα and ABCA1. These results demonstrate that lycopene can inhibit DU145 cell proliferation via PPARγ-LXRα-ABCA1 pathway and that lycopene and T0901317 exhibit synergistic effects.
authors.affiliation: Department of Food Science and Biotechnology, National Chung Hsing University, Taichung 402, Taiwan ROC.
authors.forename: Chih-Min
authors.initials: CM
authors.lastname: Yang
authors.forename: Ya-Ling
authors.initials: YL
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; D000230:Adenocarcinoma / Q000178:diet therapy / Q000188:drug therapy* / Q000378:metabolism; D000970:Antineoplastic Agents / Q000819:agonists / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000819:agonists / Q000378:metabolism; D002338:Carotenoids / Q000819:agonists / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002784:Cholesterol / Q000378:metabolism; D019587:Dietary Supplements; D018565:Food-Drug Interactions; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D006845:Hydrocarbons, Fluorinated / Q000819:agonists / Q000494:pharmacology*; D000071518:Liver X Receptors; D000077276:Lycopene; D008297:Male; D009363:Neoplasm Proteins / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D057093:Orphan Nuclear Receptors / Q000819:agonists* / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D009994:Osmolar Concentration; D047495:PPAR gamma / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000178:diet therapy / Q000188:drug therapy* / Q000378:metabolism; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering; D013449:Sulfonamides / Q000819:agonists / Q000494:pharmacology*; D005466:Fluorocarbons; D000096926:Benzenesulfonamides
chemical_list: D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D002338:Carotenoids; D002784:Cholesterol; D006845:Hydrocarbons, Fluorinated; D000071518:Liver X Receptors; D000077276:Lycopene; D009363:Neoplasm Proteins; D057093:Orphan Nuclear Receptors; D047495:PPAR gamma; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D013449:Sulfonamides; C577836:ABCA1 protein, human; C000605213:NR1H3 protein, human; C423915:T0901317; D005466:Fluorocarbons; D000096926:Benzenesulfonamides