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 g/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 kappa-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.
Lin
Shwu-Yuann
SY
Department of Food Nutrition, Chung Hwa College of Medical Technology, Tainan, Taiwan, ROC.
Tsai
Shun-Jen
SJ
Wang
Lien-Hui
LH
Wu
Ming-Fang
MF
Lee
Huei
H
D000230:Adenocarcinoma / Q000453:epidemiology / Q000209:etiology / Q000517:prevention & control*; D020552:Comet Assay; D003296:Cooking; D051546:Cyclooxygenase 2; D004249:DNA Damage; D004305:Dose-Response Relationship, Drug; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D015151:Immunoblotting; D007527:Isoenzymes / Q000187:drug effects / Q000378:metabolism*; D008175:Lung Neoplasms / Q000453:epidemiology / Q000209:etiology / Q000517:prevention & control*; D008565:Membrane Proteins; D010938:Plant Oils / Q000009:adverse effects*; D011451:Prostaglandin-Endoperoxide Synthases / Q000187:drug effects / Q000378:metabolism*; D011794:Quercetin / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013624:Taiwan / Q000453:epidemiology; D014407:Tumor Cells, Cultured
D007527:Isoenzymes; D008565:Membrane Proteins; D010938:Plant Oils; D012333:RNA, Messenger; D011794:Quercetin; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases