Quercetin metabolites inhibit MMP-2 expression in A549 lung cancer cells by PPAR-γ associated mechanisms.
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 10μM quercetin and 20μM 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.
Department of Nutrition, Hung Kuang University, No. 1018 Sec. 6 Taiwan Boulevard, Taichung, 43302, Taiwan, ROC. Electronic address: chchuang@hk.edu.tw.
Cheng-Hung
CH
Chuang
Department of Nutrition, Hung Kuang University, No. 1018 Sec. 6 Taiwan Boulevard, Taichung, 43302, Taiwan, ROC.
Chiao-Lin
CL
Yeh
Institute of Nutritional Science, Chung Shan Medical University, No. 110 Sec. 1 Jianguo N. Rd, Taichung, 402, Taiwan, ROC.
Shu-Lan
SL
Yeh
Department of Beauty Science, National Taichung University of Science and Technology, No. 193, Sec. 1, San-Min Rd., Taichung, 40343, Taiwan, ROC.
En-Shyh
ES
Lin
Department of Biotechnology, Hung Kuang University, No. 1018 Sec. 6 Taiwan Boulevard, Taichung, 43302, Taiwan, ROC.
Li-Yu
LY
Wang
Department of Nutrition, Hung Kuang University, No. 1018 Sec. 6 Taiwan Boulevard, Taichung, 43302, Taiwan, ROC.
Ying-Hsuna
YH
Wang
D000072283:A549 Cells; D000813:Anilides / Q000494:pharmacology; D000818:Animals; D016588:Anticarcinogenic Agents / Q000008:administration & dosage / Q000378:metabolism* / Q000494:pharmacology; D002465:Cell Movement / Q000187:drug effects; D002839:Chromans / Q000494:pharmacology; D019587:Dietary Supplements; D004794:Enzyme Repression / Q000187:drug effects; D016195:G2 Phase / Q000187:drug effects; D005849:Gerbillinae; D020719:Glucuronides / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism*; D006801:Humans; D008024:Ligands; D008175:Lung Neoplasms / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D009361:Neoplasm Invasiveness / Q000473:pathology / Q000517:prevention & control; D009363:Neoplasm Proteins / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D047495:PPAR gamma / Q000819:agonists* / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D011794:Quercetin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism; D034622:RNA Interference; D045162:Thiazolidinediones / Q000494:pharmacology; D000077288:Troglitazone; D015854:Up-Regulation / Q000187:drug effects
C457499:2-chloro-5-nitrobenzanilide; D000813:Anilides; D016588:Anticarcinogenic Agents; D002839:Chromans; D020719:Glucuronides; D008024:Ligands; D009363:Neoplasm Proteins; D047495:PPAR gamma; D045162:Thiazolidinediones; C531389:quercetin 3'-sulfate; C443401:quercetin 3-O-glucuronide; D011794:Quercetin; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; D000077288:Troglitazone
Lung cancer cells; Metastasis; Peroxisome proliferator-activated receptor gamma; Quercetin-3-glucuronide; Quercetin-3′-sulfate; nm23-H1