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 Overview of mechanisms of action of lycopene Heber D; Lu QYExp Biol Med (Maywood)  2002[Nov]; 227 (10): 920-3Dietary intakes of tomatoes and tomato products containing lycopene have been  shown to be associated with decreased risk of chronic diseases such as cancer and  cardiovascular diseases in numerous studies. Serum and tissue lycopene levels  have also been inversely related to the risk of lung and prostate cancers.  Lycopene functions as a very potent antioxidant, and this is clearly a major  important mechanism of lycopene action. In this regard, lycopene can trap singlet  oxygen and reduce mutagenesis in the Ames test. However, evidence is accumulating  for other mechanisms as well. Lycopene at physiological concentrations can  inhibit human cancer cell growth by interfering with growth factor receptor  signaling and cell cycle progression specifically in prostate cancer cells  without evidence of toxic effects or apoptosis of cells. Studies using human and  animal cells have identified a gene, connexin 43, whose expression is upregulated  by lycopene and which allows direct intercellular gap junctional communication  (GJC). GJC is deficient in many human tumors and its restoration or upregulation  is associated with decreased proliferation. The combination of low concentrations  of lycopene with 1,25-dihydroxyvitamin D3 exhibits a synergistic effect on cell  proliferation and differentiation and an additive effect on cell cycle  progression in the HL-60 promyelocytic leukemia cell line, suggesting some  interaction at a nuclear or subcellular level. The combination of lycopene and  lutein synergistically interact as antioxidants, and this may relate to specific  positioning of different carotenoids in membranes. This review will focus on the  growing body of evidence that carotenoids have unexpected biologic effects in  experimental systems, some of which may contribute to their cancer preventive  properties in models of carcinogenesis. Consideration of solubility in vitro,  comparison with doses achieved in humans by dietary means, interactions with  other phytochemicals, and other potential mechanisms such as stimulation of  xenobiotic metabolism, inhibition of cholesterogenesis, modulation of  cyclooxygenase pathways, and inhibition of inflammation will be considered. This  review will point out areas for future research where more evidence is needed on  the effects of lycopene on the etiology of chronic disease.|Animals[MESH]|Anticarcinogenic Agents/*metabolism/pharmacology[MESH]|Antioxidants/*metabolism/pharmacology[MESH]|Carotenoids/*metabolism/*pharmacology[MESH]|Cell Differentiation/drug effects[MESH]|Cholesterol/metabolism[MESH]|Epidemiologic Studies[MESH]|Humans[MESH]|Inflammation[MESH]|Lycopene[MESH]|Oxidative Stress/drug effects[MESH]|Solanum lycopersicum/chemistry[MESH]|Xenobiotics/metabolism[MESH]
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