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β‐Cryptoxanthin suppresses the growth of immortalized human bronchial epithelial cells and non‐small‐cell lung cancer cells and up‐regulates retinoic acid receptor β expression

Recent findings of an inverse association between β‐cryptoxanthin and lung cancer risk in several observational epidemiologic studies suggest that β‐cryptoxanthin could potentially act as a chemopreventive agent against lung cancer. However, the biological activity of β‐cryptoxanthin and molecular mechanism(s) by which β‐cryptoxanthin affects lung tumourigenesis have not been studied. In the present study, we found that β‐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. β‐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 theG1/G0 phase and decreased those in the S phase of the cell cycle. Consistent with inhibition of the lung cancer cell growth, β‐cryptoxanthin induced the mRNA levels of retinoic acid receptor β (RARβ) in BEAS‐2B cells, although this effect was less pronounced in A549 cells. Furthermore, β‐cryptoxanthin transactivated RAR‐mediated transcription activity of the retinoic acid response element. These findings suggest a mechanism of anti‐proliferative action of β‐cryptoxanthin and indicate that β‐cryptoxanthin may be a promising chemopreventive agent against lung cancer. © 2006 Wiley‐Liss, Inc.