Lycopene proliferation

Ben-Dor, A. et al.. Effects of acyclo-retinoic acid and lycopene on activation of the retinoic acid receptor and proliferation of mammary cancer cells. Arch. Biochem. Biophys., 391, 295, 2001. 

Pastori, M. et al., Lycopene in association with alpha-tocopherol inhibits at physiological concentrations proliferation of prostate carcinoma cells, Biochem. Biophys. Res. Com., 250, 582, 1998. 

Gunasekera, RS, Sewgobind, K, Desai, S, Dunn, L, Black, HS, McKeehan, WL, and Patil, B, 2007. Lycopene and lutein inhibit proliferation in rat prostate carcinoma cells. Nutr Cancer 58, 171-177. 

Levy, J., E. Bosin, B. Feldman et al. 1995. Lycopene is a more potent inhibitor of human cancer cell proliferation than either alpha-carotene or beta-carotene. Nutr Cancer 24(3) 257-266. 

Liu, C., R. M. Russell, and X. D. Wang. 2006. Lycopene supplementation prevents smoke-induced changes in p53, p53 phosphorylation, cell proliferation, and apoptosis in the gastric mucosa of ferrets. J Nutr 136(1) 106—111. 

Livny, O., I. Kaplan, R. Reifen et al. 2002. Lycopene inhibits proliferation and enhances gap-junction communication of KB-1 human oral tumor cells. J Nutr 132(12) 3754—3759. 

Salman, H., M. Bergman, M. Djaldetti, and H. Bessler. 2007. Lycopene affects proliferation and apoptosis of four malignant cell lines. Biomed Pharmacother 61(6) 366-369. 

Lycopene Effects on Proliferation, Cell Cycle, and Apoptosis.445... 

In summary, unoxidized lycopene can act as a lipid and a DNA antioxidant at physiological concentrations but oxidized lycopene or high concentrations of lycopene, and depending upon the oxidizing conditions, may increase lipid peroxidation and oxidative DNA damage. Furthermore, the pro-oxidant effects may result in an increased apoptosis and a decreased cell viability, which should be kept in mind as studies on proliferation and apoptosis are reviewed. 

Barber et al. (2006) Primary benign epithelial cells (PECs) isolated at the time of surgery in = 6) PSA-secreting LNCaP used as l-20pM lycopene (Sigma) THF 48 h Proliferation measured as BrdU incorporation into DNA... 

Obermuller-Jevic et al. (2003) comparison PrEC-non-neoplastic cells M -trans/5% cis isomers 0.5—5.0pM THF affected cell cycle, corrected for THF alone values 48 h medium changed every 24 h Lycopene uptake 3H thymidine incorporation for proliferation... 

PC-3 lycopene, water BHT times 24, Cell proliferation Decreased by 15% at 1 pM in LNCaP for Lycopen ... 

There are several alternative pathways associated with the balance between proliferation and apoptosis that are affected by lycopene treatment, especially the insulin-like growth factor (IGF) signaling pathway. Another is the possibility that lycopene or one of its breakdown products has retinoid activity. Kotake-Nara et al. compared acyclo-retinoic acid, an in vitro oxidation product of lycopene, to four actively researched anticarcinogenic retinoids. Acycloretinoic acid was found to more actively reduce PC-3 and DU-145 cell viabilities (but not LNCaP) through apoptosis in a medium already containing small amounts of natural retinoids. But study concentrations were 20 pM, far above physiologically relevant lycopene concentrations, let alone the smaller concentration of one of its breakdown products. Acycloretinoic acid had a very low affinity for the retinoid X receptors (RXR) and retinoic acid receptors (RAR) receptors (Kotake-Nara et al. 2002). 

Lycopene treatment appears to have other bioactivities that do not fall into the broad category of the modulation of cell proliferation or apoptosis. Only those that have been explored in prostate cell lines are discussed below. 

Similarly, lycopene was also able to inhibit cell cycle progression at the G0/G1 phase and to reduce cell proliferation by a mechanism involving cyclin Dl in normal cells. It has been reported that, after the stimulation of synchronized human normal prostate epithelial cells with growth factors, cyclin Dl protein expression increases in lycopene-untreated cells. Such an increase was lower or even absent following treatment with lycopene at the concentration of 0.5mmol/L and 5.0mmol/L, respectively. Interestingly, it was specific for cyclin Dl, since cyclin E levels remained constant and were unaffected by lycopene treatment (Obermiiller-Jevic et al., 2003). 

Although the influence of lycopene and proliferation of carcinoma cells appears not limited to its ability to modulate Cx43 expression, lycopene as well as its oxidation products have been reported to enhance GJC in cultured cells (Livny et al., 2002 Stahl et al., 2000). Recent data indicate that lycopene may indeed increase connexin-43 expression in human prostate (Kucuk et al., 2001). 

Kim, L., Rao, A.V., and Rao, L.G. 2003. Lycopene II-effect on osteoblasts The carotenoid lycopene stimulates cell proliferation and alkaline phosphatase activity of SaOS-2 cells. J Med Food 6 79-86. 

Wang, A. and Zhang L. 2007. Effect of lycopene on proliferation and cell cycle of hormone refractory prostate cancer PC-3 cell line. Wei Sheng Yan Jiu 36 575-578. 

Cell cycle by flow cytometry Apoptosis by flow cytometry Lycopene uptake Proliferation by BrdU... 

Tang FY, Cho HJ, Pai MH and Chen YH. 2008. Concomitant supplementation of lycopene and eicosapen-taenoic acid inhibits the proliferation of human colon cancer cells. J Nutr Biochem. In press. 

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