Quercetin metabolites inhibit MMP-2 expression in A549 lung cancer cells by PPAR-γ associated mechanisms

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• 作者：Cheng-Hung Chuang^a ; ^{chchuang@hk.edu.tw" class="auth_mail" title="E-mail the corresponding author} ; Chiao-Lin Yeh^a ; Shu-Lan Yeh^b ; En-Shyh Lin^c ; Li-Yu Wang^d ; Ying-Hsuna Wang^a
• 关键词：Q3G ; Quercetin-3-glucuronide ; Q3&prime ; S ; Quercetin-3&prime ; -sulfate ; TGZ ; Troglitazone ; MMP-2 ; Matrix metalloproteinases-2 ; PPAR-γ ; Peroxisome proliferator-activated receptor gamma ; TIMP-2 ; Tissue inhibitor of metalloproteinase 2 ; QP ; quercetin-metabolite-enriched plasma ; CP ; control plasma
• 刊名：Journal of Nutritional Biochemistry
• 出版年：2016
• 出版时间：July 2016
• 年：2016
• 卷：33
• 期：Complete
• 页码：45-53
• 全文大小：1087 K

文摘

Our previous study demonstrated that quercetin-metabolite-enriched plasma (QP) but not quercetin itself upregulates peroxisome proliferator-activated receptor gamma (PPAR-γ) expression to induce G₂/M arrest in A549 cells. In the present study, we incubated A549 cells with QP as well as quercetin-3-glucuronide (Q3G) and quercetin-3′-sulfate (Q3′S), two major metabolites of quercetin, to investigate the effects of quercetin metabolites on cell invasion and migration, the possible mechanisms and the role of PPAR-γ. We also compared the effects of QP with those of quercetin and troglitazone (TGZ), a PPAR-γ ligand. The results showed that QP significantly suppressed cell invasion and migration, as well as matrix metalloproteinases (MMPs)-2 activity and expression in a dose-dependent manner. The effects of 10% QP on those parameters were similar to those of 10 μM quercetin and 20 μM TGZ. However, QP and TGZ rather than quercetin itself increased the expressions of nm23-H1 and tissue inhibitor of metalloproteinase (TIMP-2). Furthermore, we demonstrated that Q3G and Q3′S also inhibited the protein expression of MMP-2. GW9662, a PPAR-γ antagonist, significantly diminished such an effect of Q3G and Q3′S. Silencing PPAR-γ expression in A549 cells also significantly diminished the suppression effect of Q3G and Q3′S on MMP-2 expression. Taken together, our study demonstrated that QP inhibited cell invasion and migration through nm23-H1/TIMP-2/MMP-2 associated mechanisms. The upregulation of PPAR-γ by quercetin metabolites such as Q3G and Q3′S could play an important role in the effects of QP.