title: Dietary carotenoids inhibit neoplastic transformation and modulate gene expression in mouse and human cells.
abstract: 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.
mesh_terms: 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
chemical_list: D012176:Retinoids; D002338:Carotenoids