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In-vitro studies about the anti-cancer effect of lycopene.


In vitro-studies have shown the anti-cancer properties of lycopene against many cancer cells, including cancer cells of prostate, stomach, lung, colon and skin.

Tumours are complex tissues composed of matrix proteins, connective tissue and inflammatory cells. Tumour progression is the result of interactions between the tumour cells and their surroundings. The anti-cancer of lycopene are explained by its inhibitory effect on migration of cancer cells [1] and its ability to reduce levels of circulating insulin-like growth factor (IGF) I [2] and to trap platelet-derived growth factor (PDGF)[3][4]. In vitro studies clearly show the anti-proliferative effect of lycopene on different types of cancer cells. Salman and co-workers investigated the effect of different concentrations of lycopene on the cell growth and apoptosis of colon cancer cells, leukemia cells and Burkitt lymphoma cells. All cell lines (one only at the highest dose) showed a dose-dependant inhibition of cell growth by lycopene. Two of the four tested cell lines also showed apoptosis after incubation with lycopene [9].

Metastasis is the spread of malignant tumor cells from one organ to another. Cancer cells can break away from a primary tumor and migrate through the lymphatic and blood vessels to settle down to grow within normal tissues elsewhere in the body. Studies have shown that lycopene inhibits tumor metastasis in vitro and in vivo. When nude mice were orally supplemented with lycopene showed ten weeks later fewer tumors after injection with human liver cancer cells. Injection of the tumor cells resulted in increased plasma levels of matrix metalloproteinase-2 and vascular endothelial growth factor. Lycopene also reduced the levels of proliferating cellular nuclear antigen, matrix metalloproteinase-9 and vascular endothelial growth factor. Lycopene considerably increased the expression of the metastasis suppressor gene nm23-h1 [1]. Intracellular communication is important in the development of cancer. An Italian study led by Fornelli demonstrated that lycopene inhibited the gap junction intercellular communication in cultured breast tumor cells and reduced cell growth [7]. These cells were treated with different doses of lycopene for a period of up to 72 hours after which the gap junction intercellular communication was assessed with a dye-transfer assay using lucifer yellow. They found that lycopene dose-dependently increased this intracellular communication and stimulated the expression of connexins (gap junction proteins).

High levels of IGF I have been linked to an increased risk of colon cancer and other cancers [2][5][9]. In-vitro studies on lung cancer cells show that drugs inhibiting the signaling function of IGF can be of potential interest in cancer therapy. Vrieling et al. tested the effect of lycopene supplementation on IGF levels in 71 individuals with a family history of colon cancer. Lycopene supplementation significantly increased levels of IGF-binding proteins (type 1 and type2) but did not alter IGF levels [2]. Overexpression of cyclin D1 is often observed in many breast cancer tumors. Nahum and co-workers investigated the effect of lycopene on cultured human breast cancer cells and found that lycopene reduced the mitogenic effect IGF1 by reducing the level of cyclin D1[9].

Walfisch and co-workers also suggest that tomato lycopene extract has a role in the prevention of colon and possibly other types of cancer. They tested the effect of a short-term lycopene intake on the serum levels of IGF system components in colon cancer patients. Patients who were supplemented with lycopene showed a 100% increase in plasma lycopene levels and a 25% increase in IGF 1 compared to the placebo group [5]. A study by the Chittaranjan National Cancer Institute in India found that the treatment of rats with lycopene reduced the number of azoxymethane-induced aberrant crypt foci by 57 percent [8]. Lycopene reduced the expression of cyclooxygenase-2 and inducible nitric oxide synthase. This reduction is related with the prevention of colon cancer.

Studies with cultured human skin fibroblasts showed that lycopene inhibited cell migration induced platelet-derived growth factor-BB. This growth factor has been suggested to stimulate tumor growth by modulating the microenvironment. Lycopene inhibited PDGF-BB-induced migration of human fibroblasts on gelatin and collagen by inhibiting PDGF-BB signaling. Lycopene induced phosphorylation of PDGF receptor beta and attenuated several kinases (extracellular signal-regulated kinase 1/2, p38 and c-Jun N-terminal kinase). Lycopene directly trapped the platelet-derived growth factor, both in-vitro and in-vivo conditions [3][4]. I may act as anti-cancer agent by inhibiting stromal cells, tumour cells and their interactions.

A study lead by Liu concluded that consumption of lycopene may reduce smoke induced changes and may protect against the development of gastric cancer [10]

[1] Huang CS, Liao JW, Hu ML. "Lycopene inhibits experimental metastasis of human hepatoma SK-Hep-1 cells in athymic nude mice." J Nutr. 2008 Mar;138(3):538-43.
[2] Vrieling A, Voskuil DW, Bonfrer JM, Korse CM, van Doorn J, Cats A, Depla AC, Timmer R, Witteman BJ, van Leeuwen FE, Van't Veer LJ, Rookus MA, Kampman E. "Lycopene supplementation elevates circulating insulin-like growth factor binding protein-1 and -2 concentrations in persons at greater risk of colorectal cancer." Am J Clin Nutr. 2007 Nov;86(5):1456-62.
[3] Chiang HS, Wu WB, Fang JY, Chen DF, Chen BH, Huang CC, Chen YT, Hung CF. "Lycopene inhibits PDGF-BB-induced signaling and migration in human dermal fibroblasts through interaction with PDGF-BB." Life Sci. 2007 Nov 10;81(21-22):1509-17.
[4] Wu WB, Chiang HS, Fang JY, Hung CF. " Inhibitory effect of lycopene on PDGF-BB-induced signalling and migration in human dermal fibroblasts: a possible target for cancer." Biochem Soc Trans. 2007 Nov;35(Pt 5):1377-8.
[5] Walfisch S, Walfisch Y, Kirilov E, Linde N, Mnitentag H, Agbaria R, Sharoni Y, Levy J. " Tomato lycopene extract supplementation decreases insulin-like growth factor-I levels in colon cancer patients." Eur J Cancer Prev. 2007 Aug;16(4):298-303.
[6] Salman H, Bergman M, Djaldetti M, Bessler H. "Lycopene affects proliferation and apoptosis of four malignant cell lines." Biomed Pharmacother. 2007 Jul;61(6):366-9.
[7] Fornelli F, Leone A, Verdesca I, Minervini F, Zacheo G. " The influence of lycopene on the proliferation of human breast cell line (MCF-7)." Toxicol In Vitro. 2007 Mar;21(2):217-23.
[8] Sengupta A, Ghosh S, Das RK, Bhattacharjee S, Bhattacharya S. " Chemopreventive potential of diallylsulfide, lycopene and theaflavin during chemically induced colon carcinogenesis in rat colon through modulation of cyclooxygenase-2 and inducible nitric oxide synthase pathways." Eur J Cancer Prev. 2006 Aug;15(4):301-5.
[9] Nahum A, Zeller L, Danilenko M, Prall OW, Watts CK, Sutherland RL, Levy J, Sharoni Y. " Lycopene inhibition of IGF-induced cancer cell growth depends on the level of cyclin D1." Eur J Nutr. 2006 Aug;45(5):275-82.
[10] Liu C, Russell RM, 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.




 
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