Protection by quercetin against cooking oil fumes-induced DNA damage in human lung adenocarcinoma CL-3 cells: Role of COX-2

Epidemiological studies have shown that the incidence of lung cancer was associated with exposure to, cooking oil fumes (COF) in nonsmoking Taiwanese women. We suspect that quercetin may be a potent inhibitor for reduction of COF-induced DNA damage and prevention of lung cancer development. Comet assay was used to evaluate the DNA damage induced by a relatively low dose of COF (100 mug/ml) in human lung adenocarcinoma CL-3 cells. To understand whether quercetin has the most potent protective effect on COF-induced DNA damage, the 50% inhibition concentration of quercetin for COF-induced DNA damage (IC50) was compared with IC50 values of alpha-naphthoflavone (alpha-NF), NS-398, and NaN3 (specific inhibitors) or scavengers of cytochrome P-450 1A1, cyclooxygenase-2 (COX-2), and reactive oxygen species. The IC50 of quercetin was only 1/2, 1/3, and 1/35 of IC50 values of alpha-NF, NS-398, and NaN3, respectively. Clearly, quercetin was the most effective inhibitor of COF-induced DNA damage, followed sequentially by a-NF, NS-398, and NaN3. To further elucidate whether inhibition of COF-induced DNA damage of quercetin is mediated through the inhibition of COX-2 gene expression by altering the nuclear factor-kappaB pathway, COX-2 mRNA and its protein expressions induced by COF were evaluated by reverse transcription-polymerase chain reaction and Western blot, respectively. Our data showed that COX-2 mRNA and protein levels were significantly repressed by addition of quercetin in a dose-dependent manner. Gel retardation assay showed that nuclear factor-kappaB DNA binding activity induced by COF was significantly inhibited by quercetin. From our previous and present studies, it is revealed that coexpression of COX-2 and cytochrome P-450 1A1 caused by COF may contribute to genomic instability in lung cancer development. Thus quercetin may act as a potent chemopreventive agent of lung cancer for nonsmoking Taiwanese women.