Beta-Cryptoxanthin reduced lung tumor multiplicity and inhibited lung cancer cells motility by down-regulating nicotinic acetylcholine receptor alpha7 expression
Menée sur un modèle murin exposé par injection à une substance chimique cancérogène, cette étude montre que la bêta-cryptoxanthine, un caroténoïde, peut réduire le nombre de tumeurs pulmonaires et inhiber la motilité des cellules cancéreuses en réduisant l'expression de la sous-unité alpha-7 du récepteur nicotinique de l'acétylcholine
Despite the consistent association between a higher intake of the provitamin A carotenoid β-cryptoxanthin (BCX) and a lower risk of lung cancer among smokers, potential mechanisms supporting BCX as a chemopreventive agent are needed. We first examined the effects of BCX on 4-[methyl nitrosamino]-1-[3-pyridyl]-1-butanone (NNK)-induced lung tumorigenesis in A/J mice. BCX supplementation was given daily to the mice starting two-weeks prior to the injection of NNK and continued 16 weeks post NNK injection. BCX supplementation resulted in a dose-dependent increase of BCX concentration in both serum and lungs of the mice without a significant alteration of vitamin A (retinol and retinyl palmitate) concentration. BCX significantly reduced the multiplicity of the NNK-induced lung tumor by 52-63% compared to the NNK-treated mice without BCX supplementation. The protective effect of BCX in the lungs was associated with reductions of both mRNA and protein of the homopentameric neuronal nicotinic acetylcholine receptor α7 (α7-nAChR), which has been implicated in lung tumorigenesis. We then conducted an in vitro cell culture study, and found that BCX treatment suppressed α7-nAChR expression and inhibited the migration and invasion of α7-nAChR-positive lung cancer cells but not in cells lacking α7-nAChR. The activities of BCX were significantly attenuated by activators of α7-nAChR/PI3K signaling or by overexpression of constitutively active PI3K. Collectively, the results suggest that BCX, inhibits lung tumorigenesis and cancer cell motility through the down-regulation of α7-nAChR/PI3K signaling, independent of its provitamin A activity. Therefore, BCX can be used as a chemopreventive agent or a chemotherapeutic compound against lung cancer.