Suppression of mouse skin papilloma by canthaxanthin and beta-carotene in vivo: possibility of the regression of tumorigenesis by carotenoids without conversion to retinoic acid.
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 beta-carotene at 200 mg/kg/day for 14 days significantly reduced the cumulative size of papillomas induced on the skin by 9,10-dimethyl-1,2-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-beta, was found in papillomas of CX- and beta-carotene-treated mice, suggesting that, like CX, beta-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.
Katsumura
N
N
First Department of Internal Medicine, Gifu University School of Medicine, Japan.
Okuno
M
M
Onogi
N
N
Moriwaki
H
H
Muto
Y
Y
Kojima
S
S
D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D016644:Canthaxanthin / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use*; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D051379:Mice; D010212:Papilloma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D018168:Receptors, Retinoic Acid / Q000235:genetics; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D014212:Tretinoin / Q000378:metabolism* / Q000494:pharmacology; D019207:beta Carotene / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use*
D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D018168:Receptors, Retinoic Acid; D019207:beta Carotene; D016644:Canthaxanthin; D014212:Tretinoin; D015127:9,10-Dimethyl-1,2-benzanthracene