58 men completed the trial. Serum lycopeneincreased 0.55 μmol/L with treatment and declined 0.29 μmol/L with placebo. We observed no meaningful differences in PSA, IGF-1 or IGFBP3 concentration between groups, nor any differences in expression of MCM-2 or p27 in epithelial nuclei. Prevalences of cancer, HGPIN, atrophy or inflammation post-treatment were similar; however, more extensive atrophy and less extensive HGPIN was more common in the lycopene group.
Dietary tomato and lycopene impact androgen signaling- and carcinogenesis-related gene expression during early TRAMP prostate carcinogenesis
Lei Wan, Hsueh-Li Tan, Jennifer M. Thomas-Ahner, Dennis K. Pearl, John W. Erdman, Jr., Nancy E. Moran, Steven K. Clinton
Consumption of tomato products containing the carotenoid lycopene is associated with a reduced risk of prostate cancer.
Expression of genes involved in androgen metabolism/signalingpathwaysarereduced by lycopene feeding (Srd5a1) and by tomato-feeding (Srd5a2, Pxn, and Srebf1). Additionally, tomato-feeding significantlyreduced expression of genes associated with stem cell features, Aldh1a and Ly6a, while lycopene-feeding significantlyreduced expression of neuroendocrine differentiation-related genes, Ngfr and Syp. Collectively, these studies demonstrate a profile of testosterone-regulated genes associated with early stages of prostate carcinogenesis that are potential mechanistic targets of dietary tomato components.
Recent Progress on Nutraceutical Research in Prostate Cancer
Yiwei Li, Aamir Ahmad, Dejuan Kong, Bin Bao, Fazlul H. Sarkar
Experimental studies have revealed that lycopene could down-regulate the expression of Ras, NF-κB, cyclin D, p-Akt, and Bcl-2, and up-regulate the expression of p21, p27, p53, and Bax in PCa cells , demonstrating that lycopenemodulates the signaling that controls cell growth and apoptotic cell death pathways. Lycopene also inhibited IGF-I signal transduction in normal prostate epithelial cells through down-regulation of DHT-stimulatedIGF-1 production . Lycopene also showed the inhibitory effects on ARsignaling in PCa. One study showed that lycopene could inhibit the activity of AR gene element and the AR expression in a dose-dependent manner . Consistent with AR inhibition, the suppression of PSA expression by lycopene was also observed, suggesting that dietary lycopene could have clinical impact in PCa.
Effect of lycopene on androgen receptor and prostate-specific antigen velocity.
Zhang X , et al.
The addition of 0.5 micromol/L, 5 micromol/L, 10 micromol/L and 15 micromol/L of lycopene was shown to inhibit cell growth by 2.66%, 4.29%, 3.73% and 13.66%, respectively, compared with the THF solvent control samples (P=0.015). As compared with the RPMI1640 medium group, cell proliferation in the presence of 5 micromol/L, 10 micromol/L, and 15 micromol/L lycopene was inhibited by 8.12%, 6.33% and 12.00%, respectively (P=0.024). We showed for the first time that lycopeneinhibited the activity of the androgen receptor gene element in a dose-related manner. Inhibition was seen in the transcription of the luciferase construct and confirmed by androgen receptor element expression assayed by Western blotting. Regression slopes of (log) PSA vs. time decreased in 26/37 (70%, 95%CI 53%-84%) of the patients after supplementation and in eight cases (21%) the post-treatment slope was negative. For these eight patients, the average fall in PSA was equivalent to 2% over 28 days (i.e. an average slope/d of -0.000713). The Wilcoxon rank-sum test showed an overall statistically significantdecrease in slope (P=0.0007). Analysis of the PSA doubling time (pretreatment vs. posttreatment) showed a median increase after supplementation for 174 days; however, this was not statistically significant (P=0.18).
Lycopene consumption is inversely related to humanprostate cancer risk and inhibits IGF-I and androgen signaling in ratprostate cancer. In this study, lycopene, in dietary concentration, reversedDHT effects of 6S cells on NPE cell death, decreased 6S cell IGF-I production by reducing AR and beta-catenin nuclear localization and inhibited IGF-I-stimulated NPE and PREC growth, perhaps by attenuating IGF-I's effects on serine phosphorylation of Akt and GSK3beta and tyrosine phosphorylation of GSK3. T
Serum testosterone is reduced following short-term phytofluene, lycopene, or tomato powder consumption in F344 rats.
Campbell JK , et al.
Sham-operated rats provided with either phytofluene, lycopene, or tomato powder had approximately 40-50% lower serum testosteroneconcentration than the sham-operated, control-fed group. Tissue and serum phytofluene and lycopeneconcentration were greater in castrated rats than in sham-operated rats, which may have been due in part to a decrease of hepatic CYP 3A1 mRNA expression and benzyloxyresorufin-O-dealkylase activity.