High intake of
lycopene has been associated with a lower risk of a variety of
cancers including
lung cancer. We recently showed that
lycopene can be converted to apo-10'-lycopenoids [Hu et al. (2006). J. Biol. Chem., 281, 19327-19338] in mammalian tissues both in vitro and in vivo, raising the question of whether apo-10'-lycopenoids have
biological activities against lung
carcinogenesis. In the present study, we report that
apo-10'-lycopenoic acid inhibited 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, inhibition of cell cycle progression from G(1) to S phase and increased cell cycle regulators p21 and p27
protein levels. In addition,
apo-10'-lycopenoic acid transactivated the
retinoic acid receptor beta (RARbeta) promoter and induced the expression of RARbeta. We further examined the effect of
apo-10'-lycopenoic acid treatment on 4-(N-methyl-N-nitrosamino)-1-(3-pyridal)-1-butanone (NNK)-induced lung
tumorigenesis in the A/J mouse model. We found that the lung
tumor multiplicity was decreased dose dependently from an average of 16
tumors per mouse in the NNK injection alone group, to an average of 10, 7 and 5
tumors per mouse in groups injected with NNK and supplemented with 10, 40 and 120 mg/kg diet of
apo-10'-lycopenoic acid, respectively. These observations demonstrate that
apo-10'-lycopenoic acid is a
biological active metabolite of
lycopene and suggest that
apo-10'-lycopenoic acid is a potential chemopreventive agent against lung
tumorigenesis.