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.

Beta-carotene alters the morphology of NCI-H69 small cell lung cancer cells.

The effect of beta-carotene on the morphology of NCI-H69 small cell lung cancer cells that had undergone beta-carotene-induced growth reduction (P < 0.05) was examined. The cells were grown at 1 x 10(8) cells/L and were cultured with or without 20 micromol/L beta-carotene. The qualitative electron microscopic observations revealed that beta-carotene-treated cells contained more vacuoles than control cells not treated with beta-carotene. The quantitative image analysis showed a significantly smaller (P < 0.05) value of the nuclear roundness factor for treated cells compared with control cells, indicating an irregular nuclear morphology of beta-carotene-treated cells. The major diameter of the cells and the minor diameter of the nuclei were significantly smaller (P < 0.05), and the nuclear perimeter was significantly larger (P < 0.05) in beta-carotene-treated cells. The ratio of nucleus to cytoplasm was significantly less (P < 0.05) in beta-carotene-treated cells compared with control cells, indicating a less malignant growth of the cells. These results demonstrate that the treatment of small cell lung cancer cells with beta-carotene induces morphological changes in the cells concomitant with a reduction in their proliferation. Further investigation is required to show a direct effect of beta-carotene or its intracellular polar metabolites on the morphology of these cells.