American Journal of Clinical Nutrition, Vol 62, 1327S-1336S, Copyright © 1995 by The American Society for Clinical Nutrition, Inc

ORIGINAL RESEARCH COMMUNICATIONS

Dietary carotenoids inhibit neoplastic transformation and modulate gene expression in mouse and human cells

JS Bertram and H Bortkiewicz
Cancer Research Center of Hawaii, University of Hawaii, Honolulu 96813, USA.

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.

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