Lycopene and vitamin E interfere with autocrine/paracrine loops in the Dunning prostate cancer model.
Epidemiological studies have consistently associated high intakes of lycopene or vitamin E with a reduced prostate cancer risk. Both compounds were tested in the MatLyLu Dunning prostate cancer model to gain insight into the in vivo action of lycopene and vitamin E. Supplementation for 4 weeks with 200 ppm lycopene, 540 ppm vitamin E, or both led to plasma levels comparable with those in humans. Both compounds also accumulated in tumor tissue. Macroscopic evaluation of the tumors by magnetic resonance imaging showed a significant increase in necrotic area in the vitamin E and the lycopene treatment groups. Microarray analysis of tumor tissues revealed that both compounds regulated local gene expression. Vitamin E reduced androgen signaling without affecting androgen metabolism. Lycopene interfered with local testosterone activation by down-regulating 5-alpha-reductase and consequently reduced steroid target genes expression (cystatin-related protein 1 and 2, prostatic spermine binding protein, prostatic steroid binding protein C1, C2 and C3 chain, probasin). In addition, lycopene down-regulated prostatic IGF-I and IL-6 expression. Based on these findings, we suggest that lycopene and vitamin E contribute to the reduction of prostate cancer by interfering with internal autocrine or paracrine loops of sex steroid hormone and growth factor activation/synthesis and signaling in the prostate.
Siler
Ulrich
U
DSM Nutritional Products, Human Nutrition and Health, Carotenoid Section, Basel, Switzerland.
Barella
Luca
L
Spitzer
Volker
V
Schnorr
Jörg
J
Lein
Michael
M
Goralczyk
Regina
R
Wertz
Karin
K
D000728:Androgens / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D019898:Autocrine Communication / Q000187:drug effects*; D001835:Body Weight; D002338:Carotenoids / Q000008:administration & dosage / Q000032:analysis / Q000097:blood / Q000494:pharmacology*; D042944:Cholestenone 5 alpha-Reductase / Q000378:metabolism; D004032:Diet; D019587:Dietary Supplements; D004195:Disease Models, Animal; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D000077276:Lycopene; D008279:Magnetic Resonance Imaging; D008297:Male; D009336:Necrosis; D020411:Oligonucleotide Array Sequence Analysis; D019899:Paracrine Communication / Q000187:drug effects*; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D051381:Rats; D014810:Vitamin E / Q000008:administration & dosage / Q000032:analysis / Q000097:blood / Q000494:pharmacology*
D000728:Androgens; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D014810:Vitamin E; D002338:Carotenoids; D007334:Insulin-Like Growth Factor I; D042944:Cholestenone 5 alpha-Reductase; D000077276:Lycopene