High-fat corn oil and olive oil diets inhibit 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced lung tumorigenesis

Cigarette smoking is the major cause of lung cancer cases worldwide and the tobacco-specific nitrosamine NNK is suggested to play an important role in tobacco-related cancers. Epidemiological and animal studies have suggested a beneficial role of olive oil consumption against lung cancer formation. In contrast, high intake of dietary fat rich in o-6 polyunsaturated fatty acids has been associated with increased risk in carcinogenesis.; In the present study, we examined the effect of high-fat corn oil (HFCO) and high-fat olive oil (HFOO) diets on NNK-induced lung tumorigenesis in A/J mice. Our results demonstrated that HFOO was more effective in inhibiting lung tumor development at the post-initiation stage than at the initiation stage. At the post-initiation stage, HFOO significantly decreased NNK-induced lung tumor multiplicity and tumor volumes by 41% and 52%, respectively. Moreover, HFOO inhibited lung tumor volumes even when administered at later time points of the post-initiation phase. HFCO diet inhibited lung tumorigenesis to a similar extent as HFOO treatment. We further investigated the effect of these two dietary fats on the expression and activities of cyclooxygenases (COXs) and lipoxygenases (LOXs), two classes of key enzymes that metabolize arachidonic acid (AA) to eicosanoids. Although HFOO diet was shown to up-regulate 12-LOX levels, both HFCO and HFOO diets led to a decreased COX-2 expression and COX activity at the time point when they were highly induced by NNK administration, with a concomitant reduction in basal PGE2 levels. In contrast, COX-1 expression was not affected by carcinogen and dietary treatment. When administered without the presence of NNK, high-fat diets alone inhibited COX-2 protein levels and basal PGE2 formation. In addition, both HFCO and HFOO diets significantly suppressed NNK-induced pulmonary hyperproliferation and induced apoptosis, the latter of which may be partially via caspase-3 activation. As compared to NNK-treated control mice, high-fat diets resulted in reduced pulmonary protein kinase C (PKC) expression and activity.; Taken together, the abilities of dietary corn oil and olive oil to modulate COX-2, cell proliferation, and apoptosis as well as PKC levels may partially contribute to their antitumorigenic effect on NNK-induced lung tumorigenesis at the post-initiation stage.