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Lycopene Stops Prlfrtn of Human Oral Ca Cells

Lycopene Inhibits Proliferation and Enhances Gap-Junction Communication of KB-1 Human Oral Tumor Cells

Orly Livny, Ilana Kaplan*, Ram Reifen, Sylvie Polak-Charcon, Zecharia Madar and Betty Schwartz1

Institute of Biochemistry, Food Science and Nutrition, Faculty of Agricultural, Food and Environmental Quality Sciences, The Hebrew University of Jerusalem, Rehovot 76100, Israel; * Department of Oral Pathology and Medicine, School of Dental Medicine, Tel-Aviv University, Tel-Aviv, Israel; and Institute of Pathology, Sheba Medical Center, Tel-Hashomer, Israel 1

To whom correspondence should be addressed. E-mail: bschwart@agri.huji.ac.il

Cell-cell interaction via gap junctions is considered to be a key factor in tissue homeostasis, and its alteration is associated with the neoplastic phenotype. Experimental and epidemiologic data suggest that carotenoids, particularly lycopene and ß-carotene, can reduce the risk of certain cancers.

The aim of this study was to assess whether lycopene and ß-carotene interfere at some stage with the carcinogenic processes in human cancer cells derived from the oral cavity. KB-1 cells, originating from a human oral cavity tumor, were incubated with different concentrations of lycopene or ß-carotene delivered via the cell culture media from stock solutions in tetrahydrofuran.

Lycopene strongly and dose dependently inhibited proliferation of KB-1 human oral tumor cells. ß-Carotene was a far less effective growth inhibitor. Lycopene (3 and 7 µmol/L) significantly upregulated both the transcription (P < 0.005) and the expression (P < 0.05) of connexin 43, a key protein in the formation of gap-junctional communication. ß-Carotene (3 µmol/L) tended to upregulate connexin 43 expression (P = 0.07) and significantly affected transcription of connexin 43 at 7 µmol/L (P < 0.05).

Gap-junctional communication measured by scrape-loading dye transfer and electron microscopy showed that lycopene enhanced gap-junctional communication between the cancer cells, whereas ß-carotene was less effective in this regard.

The pattern of cellular uptake and incorporation into cancer KB-1 cells differed significantly between the carotenoids. ß-Carotene was avidly and rapidly incorporated into KB-1 cells, whereas lycopene uptake into the cells took place after longer incubation periods and only at the highest concentrations.

The results of the present study further support the hypothesis that carotenoids in general, and lycopene in particular, may be effective anticarcinogenic agents in oral carcinogenesis.

J. Nutr. 132:3754-3759, December 2002


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