Plasma Rich in Quercetin Metabolites Induces G₂/M Arrest by Upregulating PPAR-γ Expression in Human A549 Lung Cancer Cells

Abstract

In this study, we incubated human A549 lung cancer cells with quercetin-metabolite-enriched plasma (QMP) obtained from Mongolian gerbils 2 h after quercetin feeding (100 mg/kg body wt/week). We investigated the effects of QMP on the growth of A549 cells and the possible mechanisms for these effects. We found that QMP but not control plasma (CP) reduced the cell growth in A549 cells. QMP led to cell cycle arrest at the G₂/M phase by downregulating the expression of cdk1 and cyclin B. QMP but not CP or quercetin itself significantly increased PPAR-γ expression (p < 0.05), which was accompanied by an increase of phosphatase and tensin homologue deleted on the chromosome ten level and a decrease of phosphorylation of Akt. Furthermore, quercetin-3-glucuronide and quercetin-3′-sulfate also significantly increased PPAR-γ expression in A549 cells. GW9662, a PPAR-γ antagonist, significantly suppressed the effects of 10 % QMP on cell proliferation and on the expression of cyclin B and cdk1. Taken together, these data suggest that the activation of PPAR-γ plays an important role, at least in part, in the antiproliferative effects of quercetin metabolites.

Key words

G₂/M arrest - peroxisome proliferator-activated receptor gamma - quercetin-3-glucuronide - quercetin-3′-sulfate - cell proliferation

References

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