Lycopene apoptosis

Ettorre et al. [19] Leukemia Trigger apoptosis Lycopene phytocomplex triggered apoptosis via a mitochondrial pathway. Redox state of cells was measured in terms of glutathione (GSH) content, but only a small percentage of cells showed GSH depletion, suggesting that the loss of GSH may be a secondary consequence of ROS generation. Moreover, LycoC pretreatment effectively increased apoptosis induced by photodynamic therapy... 

Zhang, H. et al., A novel cleavage product formed by autoxidation of lycopene induces apoptosis in HL-60 cells.. Free Radic. Biol. Med., 35, 1653, 2003. 

The ozonolysis of carotenoids was employed in order to obtain oxygenated cleavage products for biological tests, for example, for lycopene. In this case, among a series of products, one product formed by a double oxidative cleavage was purified and characterized as ( , ,/ )- 4 - methyl - 8 -oxo-2,4,6-nonatrienal, and it was shown to be active in the induction of apoptosis in HL-60 cells (Zhang et al. 2003). 

Hantz, H. L., L. F. Young, and K. R. Martin. 2005. Physiologically attainable concentrations of lycopene induce mitochondrial apoptosis in LNCaP human prostate cancer cells. Exp Biol Med (Maywood) 230(3) 171-179. 

Hwang, E. S. and P. E. Bowen. 2004. Cell cycle arrest and induction of apoptosis by lycopene in LNCaP human prostate cancer cells. J Med Food 7(3) 284-289. 

Liu, C., F. Lian, D. E. Smith, R. M. Russell, and X. D. Wang. 2003. Lycopene supplementation inhibits lung squamous metaplasia and induces apoptosis via up-regulating insulin-like growth factor-binding protein 3 in cigarette smoke-exposed ferrets. Cancer Res 63(12) 3138-3144. 

Palozza, P, A. Sheriff, S. Serini et al. 2005. Lycopene induces apoptosis in immortalized fibroblasts exposed to tobacco smoke condensate through arresting cell cycle and down-regulating cyclin Dl, pAKT and pBad. Apoptosis 10(6) 1445-1456. 

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. 

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. 

Ivonov, NI, SP Cowell, P Brown, PS Rennie, ES Guns, and ME Cox. 2007. Lycopene differentially induces quiescence and apoptosis in adrogen-responsive and -independent prostate cell lines. Clin Nutr 26 252-263. 

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

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

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