各種quercetin代謝產物對Benzo[a]pyrene單獨或合併β-carotene誘發的A549細胞傷害及Cytochrome P4501A1/1A2 表現之抑制作用

Abstract

Abstract Quercetin, a flavonoid, is found ubiquitously in vegetables and fruits. In vitro studies show that quercetin may possess anticancer activity. In our previous study, the results show that quercetin attenuated the harmful effect of β-carotene (BC) induced by benzo[a]pyrene (BaP) through suppressing the expression of cytochrome P450 (CYP) 1A2. However, quercetin aglycone is little (or not) present in the plasma of humans due to its efficient phase II metabolism. Regarding the bioactivities of the conjugated metabolites of quercetin, little has been known. Thus, in this study we used A549 cells, a human lung cell line, to investigate the interaction between each metabolites of quercetin or the mixture (Q3’S: Q3G: I/2:2:1) and BC in the presence of BaP. A549 cells were pre-incubated with 2, 5 or 10 μM quercetin -3-glucuronide (Q3G), quercetin-3’-sulfate (Q3’S) and isorhamnetin (I) alone or in combination with 20 μM BC for 4 hours, followed by incubation with 20 μM benzo[a]pyrene (BaP) for 24 hours. Then, the cell viability, DNA damage, the expression of CYP 1A1/1A2 and the production of intracellular reactive oxygen species (ROS) were examined. We also compared the results with that of quercetin. In addition, we investigate the preventive effect of those quercetin metabolites on the consumption of BC induced by the oxidant, Fe/NTA. The results showed Q3G, Q3’S and I significantly inhibited the cell death and DNA damage induced by BaP or BaP+BC. The efficiencies of those metabolites were similar to that quercetin itself. Those metabolites also decreased the expression of CYP1A1/1A2 induced by BaP or BaP+BC in the order Q3’S, Q3G≧quercetin, I. However, only Q3G and Q3’S at 10 μM decreased the production of ROS induced by BaP. Q3G and quercetin had a similar effect on decreasing the consumption of BC induced by Fe/NTA. Furthermore, we found the mixture of quercetin metabolites tended to additively decrease the cytotoxicity and the expression of CYP1A1/1A2 induced by BaP or BaP+BC. Taken together, our results showed that Q3G, Q3’S and I could inhibit cell death, DNA damage and the expression of CYP1A1/1A2 induced by BaP or BaP+BC, and the efficiencies were similar to or better than that of quercetin itself. However, only Q3G significantly decreased the consumption of BC induced by the oxidant, implying that those metabolites of quercetin may interact with BC directly or indirectly.