Dietary carotenoids inhibit neoplastic transformation and modulate gene expression in mouse and human cells.
Many epidemiologic studies have associated the consumption of diets rich in fruit and green and yellow vegetables with a decreased risk of cancer. Of the many components of such a diet, the content of carotenoids, particularly beta-carotene, has been most consistently linked to decreased risk. The biological mechanism for such protection is currently unclear. Multiple possibilities exist: carotenoids are potent antioxidants and oxidative stress is known to contribute to carcinogenesis; many carotenoids can be converted to retinoids, these are known cancer preventive agents at several anatomic sites; and carotenoids may possess additional actions in mammalian cells. In a model in vitro system we showed that carotenoids both with and without provitamin A activity inhibit carcinogen-induced neoplastic transformation, inhibit plasma membrane lipid oxidation, and cause up-regulated expression of connexin 43, a gene coding for the structural unit of a gap junction. This last activity was statistically correlated with the ability to inhibit neoplastic transformation. Activity has also been shown in human cells: in fibroblasts CONNEXIN 43 expression is also up-regulated whereas in human keratinocytes grown in organotypic culture beta-carotene and canthaxanthin modulate differentiation in a manner qualitatively similar to that of retinoids. These results strongly suggest that carotenoids have intrinsic cancer chemopreventive action in humans.
D000818:Animals; D002338:Carotenoids / Q000494:pharmacology*; D002450:Cell Communication / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000187:drug effects*; D002478:Cells, Cultured; D017629:Gap Junctions / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects; D015227:Lipid Peroxidation / Q000187:drug effects; D051379:Mice; D012176:Retinoids / Q000494:pharmacology
D012176:Retinoids; D002338:Carotenoids