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 μg/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 α-naphthoflavone (α-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 α-NF, NS-398, and NaN₃, respectively. Clearly, quercetin was the most effective inhibitor of COF-induced DNA damage, followed sequentially by α-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-κB 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-κB 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.