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Lycopene and androgen effects on LNCaP cell growth and gene expression.
Author(s) -
Trasino Steven E,
Wang Thomas T.Y.,
Harrison Earl H.
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a165-b
Subject(s) - lncap , androgen receptor , androgen , lycopene , endocrinology , medicine , prostate cancer , dihydrotestosterone , cell growth , biology , chemistry , cancer research , cancer , biochemistry , hormone , antioxidant
LNCaP cells are a human, androgen‐dependent, prostate cancer cell line. We report here the effects of physiologically‐relevant concentrations of lycopene (0.1 to 5 micromolar) on androgen‐regulated cell growth and gene expression (assessed by real‐time PCR assay of mRNA levels). Lycopene treatment led to a concentration‐dependent decrease in androgen (10 nM DHT, dihydrotestosterone) ‐stimulated cell growth, an effect that was complete at 5 microM lycopene. Lycopene treatment also led to partial inhibition of the androgen‐stimulated expression of prostate specific antigen (PSA) and insulin‐like growth factor 1 receptor (IGF1‐R). Additionally, lycopene enhanced IGF‐binding protein 3 expression, which, taken together with its ability to downregulate the expression of the receptor, suggests inhibition of the IGF‐stimulated growth axis. In the absence of androgen, LNCaP cells express beta‐carotene oxygenase 2 (BCO2) but not BCO1, and they express retinaldehyde dehydrogenase 3 (ALDH1A3), but not ALDH1A2 or ALDH1A1. Lycopene treatment alone leads to a dose‐dependent stimulation of BCO2 expression. Androgen treatment leads to a marked inhibition of BCO2 expression that is largely reversed by co‐treatment with lycopene. Treatment with either lycopene or androgen alone leads to a marked stimulation of ALDH1A3 expression and these effects are additive. Lycopene may regulate the androgen‐stimulated program of gene expression in prostate cancer cells by being metabolized to apolycopenals (via BCO2) and apolycopenoic acids (via subsequent metabolism by ALDH1A3). However, direct evidence of such metabolism remains to be demonstrated.