Quantitative analysis of lycopene and its role in prostate cancer chemoprevention

Lycopene, which is a major carotenoid present in tomatoes, has been under investigation as a potential chemopreventive agent in prostate cancer. Investigation of lycopene role in the prevention of prostate cancer requires a sensitive and selective method for quantitation of lycopene in biological samples. As a part of this dissertation, fragmentation patterns of several major carotenoids, including lycopene were investigated using APCI tandem mass spectrometry. As a result of this investigation, a novel HPLC-MS-MS assay for quantitation of lycopene in biological samples was developed and validated. This assay is currently the most selective method for the quantitative analysis of total lycopene and its geometrical isomers in biological samples. The method was successfully applied to the clinical investigation of in vivo antioxidant properties of lycopene and to the in vitro studies of lycopene effect on human prostate cancer cell lines.; As a part of in vitro studies, the time course of lycopene uptake by human prostate cancer cells and the effects of lycopene on cell proliferation, prevention of lipid peroxidation, and secretion of PSA by LNCaP cells were investigated. Since androgens and androgen receptor are implicated in the development and growth of prostate cancers we also addressed hypothesis that lycopene might modulate this system.; The clinical study presented as a part of this dissertation was a four-arm, randomized, placebo-controlled, double-blind clinical intervention trial of the effects of lycopene in 120 men with prostate cancer or benign prostate hyperplasia. The specific aims of this investigation were to determine the effects of lycopene supplementation on plasma and prostate tissue levels of lycopene, prevention of DNA oxidation in leukocytes and prostate tissue, and on total PSA and the percent free PSA levels in blood. Lycopene supplementation resulted in a significant (two-fold) increase in mean plasma and prostate tissue lycopene concentrations compared to the intervention with placebo. However, no significant effect of lycopene supplementation on the extent of DNA oxidation in leukocytes and prostate tissue biopsies was observed compared to placebo. In addition, supplementation with lycopene did not have an effect on total PSA concentration and percent free PSA in plasma.