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Epidemiological evidence links lycopene consumption with decreased prostate cancer risk. Several signaling pathways have been identified as players in prostate cancer development. Chronic prostatitis, for example, due to infections, is a suggested risk factor for prostate cancer. Endogenous production of reactive oxygen species during inflammation may lead to oxidative DNA damage, which can be mutagenic, if unrepaired. Androgen signaling, cytokine (IL-6, IL-4) and growth factor signaling (e.g., IGF, Wnt/β-catenin) cross-talk via PI3K/Akt, MAPK, and Jak/STAT pathways have been identified as major controllers of prostate growth. During disease progression, and after androgen ablation therapy, the remaining operational pathways are upregulated to compensate for the lost growth signal, finally resulting in androgen-independent prostate cancer. Lycopene modulates several of the aforementioned pathways, providing a promising rationale for prostate cancer risk reduction by lycopene: In many experimental setups, lycopene reduced inflammatory signals, prevented oxidative DNA damage, modulated the expression or activity of IGF axis members, of Wnt/β-catenin and androgen signalling, and enhanced gap junctional communication. Lycopene's influence on these pathways likely contributes to the observed cell growth inhibition and apoptosis induction by lycopene. A substantial part of the lycopene effects can be explained by its antioxidant action, but other mechanisms might also be involved. [ABSTRACT FROM AUTHOR]

Abstract: A number of epidemiological studies have reported associations of β-carotene plasma levels or intake with decreased lung cancer risk. However, intervention studies in smokers reported increased lung tumor rates after high long-term β-carotene supplementation. For insight into these conflicting results, we studied the influence of β-carotene on tobacco smoke carcinogen-induced lung cancer development in the A/J-mouse using 4-(N-Methyl-N-nitro samino)-1-(3-pyridyl)-1-butanone (NNK) as the initiator and lung adenoma multiplicity as the functional endpoint. Gene regulation of the putative tumor suppressor RARβ in mouse lung was analyzed by quantitative real-time reverse transcriptase-polymerase chain reaction (RT-PCR) for its relevance in predicting the endpoint of lung cancer. A/J-mice achieved plasma β-carotene levels of up to 3 μmol/L within 4 wk and up to 6 μmol/L after 6 mo of supplementation on a diet modified to enhance β-carotene absorption. Despite high lung β-carotene concentrations of up to 6 μmol/kg, tumor multiplicity was not significantly affected by the β-carotene treatment, either in carcinogen-initiated or non-initiated mice, and was unrelated to β-carotene dose and the time point of treatment during cancer formation. Tumor multiplicity did not correlate with β-carotene plasma levels in NNK-treated animals. All RARβ isoforms were significantly suppressed in the lungs of NNK- and NNK plus high dose β-carotene-treated animals. However, the number of tumors per mouse did not correlate with the RARβ-isoform expression levels. β-carotene alone after 3 mo of supplementation mildly but significantly increased levels of RARβ1, β2, and β4. This increase persisted for 6 mo for RARβ2 and β4. In summary, we found no effect of β-carotene on tumor formation in the NNK-initiated A/J-mouse lung cancer model with respect to dose or time point of treatment. β-Carotene-induced changes in RARβ isoform gene expression levels were not predictive for the number of lung tumors but were indicative of intact β-carotene metabolism and persistent sensitivity to retinoic acid in the mice. Down-regulation of RARβ in NNK-induced adenoma-bearing lungs was similar to that observed in human lung cancer and further confirms the A/J-mouse as a valuable model for lung carcinogenesis. [ABSTRACT FROM AUTHOR]