Apo-10'-lycopenoic acid suppresses lung cancer cell growth by activating retinoic acid receptor β in vitro, and inhibits lung tumorigenesis in vivo in the A/J mouse model.

Fifth AACR International Conference on Frontiers in Cancer Prevention Research, Nov 12-15, 2006 A76 Lycopene, which has been associated with a lower risk of a variety of cancers including lung cancer, can be cleaved enzymatically at its 9',10'-double bond and converted into apo-10'-lycopenoids both in vivo and in vitro . Here, we evaluated the potential chemopreventive effect of apo-10'-lycopenoic acid against lung tumorigenesis using the A/J mouse model. We show that the apo-10'-lycopenoic acid treatment significantly increased plasma concentrations of apo-10'-lycopenoic acid, and it significantly reduced lung tumor multiplicity (32.7 to 65.4% reduction) in A/J mice in a dose-dependent manner. We additionally demonstrate that apo-10'-lycopenoic acid inhibits the growth of NHBE normal human bronchial epithelial cells, BEAS-2B immortalized normal bronchial epithelial cells, and A549 non-small cell lung cancer cells. This inhibitory effect of apo-10'-lycopenoic acid was associated with decreased cyclin E and inhibition of cell cycle progression from G1 to S phase, and increased cell cycle regulators p21 and p27 protein levels. Furthermore, apo-10'-lycopenoic acid transactivated the retinoic acid receptor β promoter and induced the expression of RARβ in these cells. Our findings suggest that apo-10'-lycopenoic acid is a potential chemopreventive agent against lung tumorigenesis, and its biological function can be mediated by the retinoid signaling pathway.