Suppression of mouse skin papilloma by canthaxanthin and β‐carotene In Vivo: Possibility of the regression of tumorigenesis by carotenoids without conversion to retinoic acid

Abstract

Using mouse skin papilloma as a model system, we examined whether the antitumorigenic activity of carotenoids was related to their provitamin A activity. Oral administration of canthaxanthin (CX) or β‐carotene at 200 mglkg/day for 14 days significantly reduced the cumulative size of papillomas induced on the skin by 9,10‐dimethyl‐l,2‐benzanthracene (p < 0.05), after the accumulation of these carotenoids in the tumors. The levels of a protooncogene, c‐myc, were simultaneously suppressed in papillomas in carotenoid‐treated mice. Because CX cannot be converted metabolically to retinoids, these results suggested that CX directly inhibited the growth of papillomas. Neither the accumulation of retinoids nor the expression of a retinoic acid‐inducible gene, retinoic acid receptor‐β, was found in papillomas of CX‐ and β‐carotene‐treated mice, suggesting that, like CX, β‐carotene might exert the tumor‐suppressing effect without being converted to retinoids. Thus a certain antitumorigenic activity of carotenoids appears not necessarily to require their provitamin A activity.