Submitted to: Cancer Prevention Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/3/2011
Publication Date: 3/18/2011
Citation: Liu, C., Bronson, R.T., Russell, R., Wang, X. 2011. Beta-Cryptoxanthin supplementation prevents cigarette smoke-induced lung inflammation, oxidative damage and squamous metaplasia in ferrets. Cancer Prevention Research. PMID:21421799. Interpretive Summary: In epidemiologic studies, high intake of beta-cryptoxanthin has been associated with a decreased risk of lung cancer, particularly among current smokers. However, data are not available from well-controlled animal studies to examine the effects of beta-cryptoxanthin on cigarette smoke-induced lung lesions, and the biological mechanisms by which beta-cryptoxanthin might affect lung carcinogenesis. In the present study, we tested two doses of beta-cryptoxanthin that are relevant to human beta-cryptoxanthin intakes and beta-cryptoxanthin supplementation at both doses significantly decreased cigarette smoke-induced lung inflammation and lung precancerous lesions. Beta-Cryptoxanthin supplementation also lowered smoke-induced expression of TNF alpha, NF-kB and AP-1 and smoke-elevated levels of oxidative DNA damage in the lungs. High-dose beta-cryptoxanthin that is equivalent to 525 ug/day in humans [within the range of intake in the Singapore Chinese Health Study] was generally more effective than low-dose beta-cryptoxanthin. Such finding thus provides useful information for the selection of the dose(s) of beta-cryptoxanthin for the potential future human beta-cryptoxanthin intervention studies.
Technical Abstract: In epidemiologic studies, high intake of beta-cryptoxanthin has been associated with a decreased risk of lung cancer, particularly among current smokers. However, data are not available from well-controlled animal studies to examine the effects of beta-cryptoxanthin on cigarette smoke-induced lung lesions, and the biological mechanisms by which beta-cryptoxanthin might affect lung carcinogenesis. We evaluated the effects of beta-cryptoxanthin supplementation on cigarette smoke-induced squamous metaplasia, inflammation, and changes in protein levels of pro-inflammatory cytokine [tumor necrosis factor alpha (TNF-alpha)] and transcription factors [nuclear factor kappa B (NF-kB) and activator protein-1 (AP-1)], as well as on smoke-induced oxidative DNA damage [8-hydroxy-2'-deoxyguanosine (8-OHdG)] in the lung tissue of ferrets. Thirty six male ferrets were assigned to cigarette smoke exposure or no exposure and to lowdose, or high-dose beta-cryptoxanthin, or no dose (2 x 3 factorial design) for 3 months. Beta-Cryptoxanthin supplementation dose-dependently increased plasma and lung beta-cryptoxanthin levels in ferrets, whereas cigarette smoke exposure lowered plasma and lung Beta-cryptoxanthin levels. Beta-Cryptoxanthin at both doses significantly decreased smoke-induced lung squamous metaplasia and inflammation. Beta-Cryptoxanthin also substantially reduced smoke-elevated TNF-alpha levels in alveolar, bronchial, bronchiolar and bronchial serous/mucous gland epithelial cells and in lung macrophages. Moreover, beta-cryptoxanthin decreased smoke-induced activation of NF-kB, expression of AP-1 and levels of 8-OHdG. The beneficial effects of beta-cryptoxanthin were stronger for high-dose beta-cryptoxanthin than for low-dose beta-cryptoxanthin. Data from this study Indicate that beta-cryptoxanthin provides a beneficial effect against cigarette smoke-induced inflammation, oxidative DNA damage and squamous metaplasia in the lungs.