Absorption and subcellular localization of lycopene in human prostate cancer cells.
Lycopene, the red pigment of the tomato, is under investigation for the chemoprevention of prostate cancer. Because dietary lycopene has been reported to concentrate in the human prostate, its uptake and subcellular localization were investigated in the controlled environment of cell culture using the human prostate cancer cell lines LNCaP, PC-3, and DU145. After 24 hours of incubation with 1.48 micromol/L lycopene, LNCaP cells accumulated 126.6 pmol lycopene/million cells, which was 2.5 times higher than PC-3 cells and 4.5 times higher than DU145 cells. Among these cell lines, only LNCaP cells express prostate-specific antigen and fully functional androgen receptor. Levels of prostate-specific antigen secreted into the incubation medium by LNCaP cells were reduced 55% as a result of lycopene treatment at 1.48 micromol/L. The binding of lycopene to the ligand-binding domain of the human androgen receptor was carried out, but lycopene was not found to be a ligand for this receptor. Next, subcellular fractionation of LNCaP cells exposed to lycopene was carried out using centrifugation and followed by liquid chromatography-tandem mass spectrometry quantitative analysis to determine the specific cellular locations of lycopene. The majority of lycopene (55%) was localized to the nuclear membranes, followed by 26% in nuclear matrix, and then 19% in microsomes. No lycopene was detected in the cytosol. These data suggest that the rapid uptake of lycopene by LNCaP cells might be facilitated by a receptor or binding protein and that lycopene is stored selectively in the nucleus of LNCaP cells.
Liu
Ang
A
Department of Medicinal Chemistry and Pharmacognosy, University of Illinois College of Pharmacy, 833 South Wood Street, M/C 781, Chicago, IL 60612-7231. Breemen@uic.edu.
Pajkovic
Natasa
N
Pang
Yan
Y
Zhu
Dongwei
D
Calamini
Barbara
B
Mesecar
Andrew L
AL
van Breemen
Richard B
RB
D016588:Anticarcinogenic Agents / Q000032:analysis / Q000378:metabolism*; D001665:Binding Sites; D002338:Carotenoids / Q000032:analysis / Q000378:metabolism*; D002467:Cell Nucleus / Q000737:chemistry / Q000378:metabolism*; D002853:Chromatography, Liquid; D006801:Humans; D007700:Kinetics; D000077276:Lycopene; D008297:Male; D013058:Mass Spectrometry; D011471:Prostatic Neoplasms / Q000737:chemistry / Q000378:metabolism*; D011944:Receptors, Androgen / Q000378:metabolism; D013997:Time Factors; D014407:Tumor Cells, Cultured
C410798:AR protein, human; D016588:Anticarcinogenic Agents; D011944:Receptors, Androgen; D002338:Carotenoids; D000077276:Lycopene