Quercetin metabolites inhibit MMP-2 expression in A549 lung cancer cells by PPAR-γ associated mechanisms |
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| Institution: | 1. Department of Nutrition, Hung Kuang University, No. 1018 Sec. 6 Taiwan Boulevard, Taichung, 43302, Taiwan, ROC;2. Institute of Nutritional Science, Chung Shan Medical University, No. 110 Sec. 1 Jianguo N. Rd, Taichung, 402, Taiwan, ROC;3. Department of Beauty Science, National Taichung University of Science and Technology, No. 193, Sec. 1, San-Min Rd., Taichung, 40343, Taiwan, ROC;4. Department of Biotechnology, Hung Kuang University, No. 1018 Sec. 6 Taiwan Boulevard, Taichung, 43302, Taiwan, ROC;1. School of Nutrition and Health Sciences, College of Nutrition, Taipei Medical University, Taipei, Taiwan;2. Master Program in Food Safety, College of Nutrition, Taipei Medical University, Taipei, Taiwan;3. Department of Anatomy and Cell Biology, College of Medicine, Taipei Medical University, Taipei, Taiwan;4. Department of Surgery, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei, Taiwan;5. Nutrition Research Center, Taipei Medical University Hospital, Taipei, Taiwan |
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| Abstract: | 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. |
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