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ARS Home » Northeast Area » Boston, Massachusetts » Jean Mayer Human Nutrition Research Center On Aging » Research » Publications at this Location » Publication #163982
Title: 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

Author
item PRAKASH, PANKAJ - TUFTS-HNRCA
item LIU, CHUN - TUFTS-HNRCA
item HU, KANGQUAN - TUFTS-HNRCA
item KRINSKY, NORMAN - TUFTS-HNRCA
item RUSSELL, ROBERT - TUFTS-HNRCA
item WANG, XIANG-DONG - TUFTS-HNRCA

Submitted to: Journal of Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/1/2003
Publication Date: 3/1/2004
Citation: PRAKASH, P., LIU, C., HU, K., KRINSKY, N.I., RUSSELL, R.M., WANG, X. 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.. JOURNAL OF NUTRITION. 2004;134:667-673.

Interpretive Summary: Low-dose beta-carotene supplementation, such as would be provided by daily consuming 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 the present study, we investigated the effects of beta-carotene, beta-apo-14'-carotenoic acid (beta-carotene metabolite), or benzo[a]pyrene (a primary lung carcinogen from cigarette smoke) treatments, either alone or in combination, on cell growth and expression of retinoic acid receptor (RAR as a tumor suppressor) of normal human bronchial epithelial (NHBE) cells. We found that both beta-carotene and beta-apo-14'-carotenoic acid significantly increased the expression of RAR-beta in the NHBE cells, prevented the reduction of RAR-beta by benzo[a]pyrene and inhibited the growth of NHBE cells with or without benzo[a]pyrene. Furthermore, beta-apo-14'-carotenoic acid has growth inhibitory effect primarily via its conversion to retinoic acid, the most active form of vitamin A. These observations indicate that the growth inhibitory effects of beta-carotene and beta-apo-carotenoic acid are through their conversion to retinoic acid and up-regulation of RAR-beta.

Technical Abstract: Low-dose beta-carotene supplementation, such as would be provided by daily consuming 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 beta-carotene, beta-apo-14'-carotenoic acid, or benzo[a]pyrene (a primary lung carcinogen from cigarette smoke) treatments, either alone or in combination, on cell growth and expression of retinoic acid receptor (RAR) of normal human bronchial epithelial (NHBE) cells. We found that both b-carotene and beta-apo-14'-carotenoic acid significantly inhibited the growth of NHBE cells (p<0.05) with or without benzo[a]pyrene. The level of RARb, a tumor suppressor, but not RAR-alpha or RAR-gamma, was reduced by 50% in the NHBE cells treated with benzo[a]pyrene. However, treatment with either beta-carotene or beta-apo-14¢-carotenoic acid significantly induced the expression of RAR-beta in the NHBE cells, and prevented the reduction of RAR-beta by benzo[a]pyrene. Furthermore, beta-apo-14'-carotenoic acid tansactivated the RAR-beta promoter primarily via its conversion to retinoic acid. In the presence of 3-mercaptopropionic acid, an inhibitor of fatty acid oxidation, both retinoic acid formation and transactivation activity from beta-apo-14'-carotenoic acid were decreased. These observations indicate that the growth inhibitory effects of beta-carotene and beta-apo-carotenoic acid are through their conversion to retinoic acid and up-regulation of RAR-beta.