Lycopene inhibits proliferation and enhances gap-junction communication of KB-1 human oral tumor cells.
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 beta-carotene, can reduce the risk of certain cancers. The aim of this study was to assess whether lycopene and beta-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 beta-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. beta-Carotene was a far less effective growth inhibitor. Lycopene (3 and 7 micro mol/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. beta-Carotene (3 micro mol/L) tended to upregulate connexin 43 expression (P = 0.07) and significantly affected transcription of connexin 43 at 7 micro mol/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 beta-carotene was less effective in this regard. The pattern of cellular uptake and incorporation into cancer KB-1 cells differed significantly between the carotenoids. beta-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.
Livny
Orly
O
Institute of Biochemistry, Food Science and Nutrition, Faculty of Agricultural, Food and Environmental Quality Sciences, The Hebrew University of Jerusalem, Rehovot 76100, Israel.
Kaplan
Ilana
I
Reifen
Ram
R
Polak-Charcon
Sylvie
S
Madar
Zecharia
Z
Schwartz
Betty
B
D001483:Base Sequence; D002338:Carotenoids / Q000494:pharmacology*; D002450:Cell Communication / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects*; D018031:Connexin 43 / Q000235:genetics / Q000378:metabolism; D017931:DNA Primers; D017629:Gap Junctions / Q000187:drug effects*; D006801:Humans; D007150:Immunohistochemistry; D000077276:Lycopene; D008854:Microscopy, Electron; D009062:Mouth Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D015854:Up-Regulation; D019207:beta Carotene / Q000494:pharmacology
D018031:Connexin 43; D017931:DNA Primers; D012333:RNA, Messenger; D019207:beta Carotene; D002338:Carotenoids; D000077276:Lycopene