Beta-carotene and beta-apo-14'-carotenoic acid prevent the reduction of retinoic acid receptor beta in benzo[a]pyrene-treated normal human bronchial epithelial cells.
Low-dose beta-carotene (BC) supplementation, such as would be provided by daily consumption of approximately 5-9 servings of fruits and vegetables, has no apparent detrimental effects, but rather appears to have a protective effect against cigarette smoke-induced lung lesions in ferrets. In the present study, we investigated the effects of BC, beta-apo-14'-carotenoic acid (14'CA), or benzo[a]pyrene (BP; a primary lung carcinogen from cigarette smoke) treatments, either alone or in combination, on cell growth and expression of the retinoic acid receptor (RAR) of normal human bronchial epithelial (NHBE) cells. We found that both BC and 14'CA inhibited the growth of NHBE cells (P < 0.05) with or without BP. The level of RARbeta, a tumor suppressor, but not RARalpha or RARgamma, was reduced by 50% in the NHBE cells treated with BP. However, treatment with either BC or 14'CA significantly induced the expression of RARbeta in the NHBE cells, and prevented the reduction of RARbeta by BP. Furthermore, 14'CA transactivated the RARbeta promoter primarily via its conversion to retinoic acid (RA). In the presence of 3-mercaptopropionic acid, an inhibitor of fatty acid oxidation, both RA formation and transactivation activity from 14'CA were decreased. These observations indicate that the growth inhibitory effects of BC and beta-apo-carotenoic acid are through their conversion to RA and upregulation of RARbeta.
Nutrition and Cancer Biology Laboratory, Jean Mayer U.S. Department of Agriculture Human Nutrition Research Center on Aging, School of Medicine, Tufts University, Boston, MA 02111, USA.
Pankaj
P
Prakash
Chun
C
Liu
Kang-Quan
KQ
Hu
Norman I
NI
Krinsky
Robert M
RM
Russell
Xiang-Dong
XD
Wang
D001564:Benzo(a)pyrene / Q000633:toxicity*; D002338:Carotenoids / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D006801:Humans; D008156:Luciferases / Q000378:metabolism; D009153:Mutagens / Q000633:toxicity; D010084:Oxidation-Reduction; D018168:Receptors, Retinoic Acid / Q000187:drug effects / Q000235:genetics*; D011994:Recombinant Proteins / Q000378:metabolism; D020545:Respiratory Mucosa / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D015533:Transcriptional Activation / Q000187:drug effects; D014162:Transfection; D019207:beta Carotene / Q000494:pharmacology*
D009153:Mutagens; D018168:Receptors, Retinoic Acid; D011994:Recombinant Proteins; C483690:apo-14'-carotenoic acid; C082925:retinoic acid receptor beta; D019207:beta Carotene; D001564:Benzo(a)pyrene; D002338:Carotenoids; D008156:Luciferases