Beta-cryptoxanthin suppresses the growth of immortalized human bronchial epithelial cells and non-small-cell lung cancer cells and up-regulates retinoic acid receptor beta expression.
Recent findings of an inverse association between beta-cryptoxanthin and lung cancer risk in several observational epidemiologic studies suggest that beta-cryptoxanthin could potentially act as a chemopreventive agent against lung cancer. However, the biological activity of beta-cryptoxanthin and molecular mechanism(s) by which beta-cryptoxanthin affects lung tumourigenesis have not been studied. In the present study, we found that beta-cryptoxanthin inhibited the growth of A549 cells, a non-small-cell lung cancer cell line and BEAS-2B cells, an immortalized human bronchial epithelial cell line in a dose-dependent manner. beta-Cryptoxanthin suppressed the protein levels of cyclin D1 and cyclin E, up-regulated the cell cycle inhibitor p21, increased the number of lung cancer cells in the G1/G0 phase and decreased those in the S phase of the cell cycle. Consistent with inhibition of the lung cancer cell growth, beta-cryptoxanthin induced the mRNA levels of retinoic acid receptor beta (RARbeta) in BEAS-2B cells, although this effect was less pronounced in A549 cells. Furthermore, beta-cryptoxanthin transactivated RAR-mediated transcription activity of the retinoic acid response element. These findings suggest a mechanism of anti-proliferative action of beta-cryptoxanthin and indicate that beta-cryptoxanthin may be a promising chemopreventive agent against lung cancer.
Lian
Fuzhi
F
Nutrition and Cancer Biology Laboratory, Jean Mayer Unite States Department of Agriculture, Human Nutrition Research Center on Aging, Tufts University, Boston, MA, USA.
Hu
Kang-Quan
KQ
Russell
Robert M
RM
Wang
Xiang-Dong
XD
D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D001483:Base Sequence; D001980:Bronchi / Q000166:cytology* / Q000187:drug effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects*; D065366:Cryptoxanthins; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D017930:Genes, Reporter; D006801:Humans; D008156:Luciferases / Q000235:genetics; D008175:Lung Neoplasms / Q000473:pathology*; D008969:Molecular Sequence Data; D018168:Receptors, Retinoic Acid / Q000235:genetics*; D020545:Respiratory Mucosa / Q000166:cytology* / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects*; D024341:Xanthophylls; D019207:beta Carotene / Q000031:analogs & derivatives* / Q000494:pharmacology
D016588:Anticarcinogenic Agents; D065366:Cryptoxanthins; D018168:Receptors, Retinoic Acid; D024341:Xanthophylls; C082925:retinoic acid receptor beta; D019207:beta Carotene; D008156:Luciferases