Carotenoids up-regulate connexin43 gene expression independent of their provitamin A or antioxidant properties.
Epidemiological evidence and studies in whole animals and cell culture have indicated that carotenoids have cancer chemopreventive action. In mouse C3H10T1/2 cells, this activity is highly correlated with the ability of carotenoids to up-regulate gap junctional intercellular communication. Here, we report that in mouse cells, carotenoids increase the expression of connexin43, a gene that encodes a major gap junction protein. This effect appears unrelated to their provitamin A or antioxidant properties, since carotenoids with and without provitamin A activity increased levels of connexin43 mRNA and protein, whereas the antioxidants methyl-bixin and alpha-tocopherol were inactive. Moreover, the active carotenoid canthaxanthin did not induce the vitamin A-inducible gene retinoic acid receptor-beta. Connexin43 is the first carotenoid-inducible gene described in mammals. By indicating an additional pathway through which carotenoids function, these data provide a mechanistic basis for cancer chemoprevention by carotenoids and may lead to a re-evaluation of carotenoid physiology.
Zhang
L X
LX
Molecular Oncology Unit, Cancer Research Center of Hawaii, University of Hawaii, Honolulu 96813.
Cooney
R V
RV
Bertram
J S
JS
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D016644:Canthaxanthin / Q000494:pharmacology; D002338:Carotenoids / Q000494:pharmacology*; D002450:Cell Communication / Q000187:drug effects; D002478:Cells, Cultured; D017630:Connexins; D005347:Fibroblasts; D005786:Gene Expression Regulation / Q000187:drug effects*; D007365:Intercellular Junctions / Q000187:drug effects; D008565:Membrane Proteins / Q000187:drug effects / Q000235:genetics*; D051379:Mice; D008809:Mice, Inbred C3H; D015854:Up-Regulation / Q000187:drug effects*; D014801:Vitamin A / Q000494:pharmacology*
D000975:Antioxidants; D017630:Connexins; D008565:Membrane Proteins; D014801:Vitamin A; D002338:Carotenoids; D016644:Canthaxanthin