β‐Cryptoxanthin supplementation inhibits carcinogen‐initiated and nicotine‐promoted lung tumor development in AJ mice

Recent epidemiologic studies show that increased dietary β‐cryptoxanthin (BCX) intake, rather than β‐carotene used in earlier human trials, is associated with reduced risk of lung cancer. However, BCX efficacy on lung carcinogenesis has not been reported. Here, we report the protective effects of different doses of BCX against lung carcinogenesis at the initiation and promotion stages in AJ mouse models. In the tobacco carcinogen NNK‐initiated lung carcinogenesis model, we found a 52–63% reduction of lung tumor multiplicity in mice pre‐treated with BCX at 0.2 and 2 mg kg BW ‐1 d ‐1 , as compared to the NNK group, P<0.01. In the NNK‐initiated and nicotine‐promoted lung cancer model, we found that nicotine not only induced emphysema, a risk for lung cancer, but also increased greatly lung tumor multiplicity of the NNK‐treated mice. Notably, BCX at 2 and 4 mg kg BW ‐1 d ‐1 prevented nicotine‐induced emphysema and decreased tumor multiplicity by 86–91%, P<0.01. BCX protection was associated with suppressions of lung AKT activation, IL‐6 and early growth response‐1 mRNA. Unlike β‐carotene reported in prior animal studies, BCX induced retinoic acid receptor‐β mRNA. By HPLC analysis, liver BCX, not retinol, increased in the BCX supplemented mice. Our data suggest that BCX is a unique chemopreventive agent for lung cancer prevention, which is likely to be independent of its provitamin A activity. Grant Funding Source : NIH R01CA104932