Plasma Rich in Quercetin Metabolites Induces G₂/M Arrest by Upregulating PPAR-γExpression 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 G (2)/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.

Oral and Intraperitoneal Administration of Quercetin Decreased Lymphocyte DNA Damage and Plasma Lipid Peroxidation Induced by TSA In Vivo

“…Consistent with previous studies [13, 14], the present study also showed that oral administration of quercetin mainly increased quercetin metabolites, especially Q3G, in the plasma of mice. In contrast, i.p.…”

“…Similar results have been observed in animal studies [13, 14]. The biochemical and biophysical properties among quercetin and quercetin metabolites may be different because of structure modification [15], although some metabolites remain physiologically active [16, 17].…”

“…The doses of quercetin administered orally were at 20 and 100 mg/kg body weight 3 times/week, which were tenfold higher than the intraperitoneal doses. Besides, in our previous study we found that the plasma, which was obtained from Mongolian gerbils 2 h after quercetin feeding by gavage at 100 mg/kg body weight/week, induced A549 cell growth arrest in vitro [14]. In addition, we also used A549 cells to compare the intracellular accumulation and the enhancing effect of quercetin and quercetin-3-glucuronide (Q3G) on the antiproliferation effect of TSA.…”

Altered Peroxisome-Proliferator Activated Receptors Expression in Human Endometrial Cancer

“…It seems highly possible, since several in vitro studies have revealed that pioglitazone, a PPAR- γ agonist, induces cell differentiation [19] and several clinical studies have demonstrated that the activation PPAR- γ increases the degree of histopathological differentiation of liposarcoma [19, 20]. However, it is not the case for all neoplastic transformation, as others demonstrated that highly malignant cancer cell lines are characterized by higher expression of PPAR γ and these data suggest that PPAR γ may act in a cancer-permissive fashion [21, 22]. …”

Anti-metastatic effects of isolinderalactone via the inhibition of MMP-2 and up regulation of NM23-H1 expression in human lung cancer A549 cells

“…Cell growth was assayed as described previously by Yeh et al (31). A549 cells were seeded in 6-well plates at a density of 1x10 5 cells/well and cultured at 37˚C for 24 and 48 h. Various concentrations of ILL werethen added to the cells to reach final concentrations of 1, 5, 10, and 20 µM in the presence of FBS.…”