A pooled analysis from well-implemented cohort studies reported that increased dietary α-cryptoxanthin (BCX) intake, rather than α-carotene used in earlier human trials, is associated with reduced risk of lung cancer. Nonetheless, BCX efficacy on lung carcinogenesis has not been reported. In these studies, we examined the protective effects of BCX at different doses against lung carcinogenesis at the initiation and the promotion stages of the cancer development in male AJ mice. In the tobacco carcinogen 4-(methylnitrosamino)- 1-(3-pyridyl)-1-butanone [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 contrast, BCX did not significantly alter the spontaneous lung tumor multiplcitiy in mice without the NNK treatment. Furthermore, in the NNK-initiated and nicotine-promoted lung cancer model, we found that nicotine treatment by intraperitoneal injections not only significantly induced emphysema, a risk for lung cancer, but also greatly increased lung tumor multiplicity of the NNK-treated mice. Remarkably, BCX at 2 and 4 mg kg BW-1 d-1 prevented the nicotine-induced pulmonary emphysema and decreased tumor multiplicity by 86-91% (P<0.01). BCX protective effect on carcinogenesis was associated with significant suppression of lung AKT activation measured by immunoblotting. BCX also reduced the emphysema-related IL-6 and early growth response-1 induction of mRNA levels measured by real-time PCR. Contrary to α-carotene reported in prior animal studies, BCX also induced the retinoic acid receptor-α mRNA. As measured by HPLC analysis, the concentrations of liver BCX were higher in the BCX supplemented mice, without alteration of the retinol concentrations. 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.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1605. doi:1538-7445.AM2012-1605