Quercetin inhibition of tumor invasion via suppressing PKC /ERK/AP-1-dependent matrix metalloproteinase-9 activation in breast carcinoma cells

Lin, Cheng; Hou, Wen Chi; Shen, Shing Chuan; Juan, Shu Hui; Ko, Ching Huai; Wang, Ling Mei; Chen, Yen Chou

doi:10.1093/carcin/bgn162

Cited by 201 publications

(142 citation statements)

References 42 publications

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“…MMP-9 was reported to be a key enzyme for degrading type IV collagen, which is a major component of the basement membrane. Elevated MMP-9 levels are functionally linked to elevated metastasis in many tumors, including brain (10), prostate (11), bladder (12) and breast (13,14). Several mechanisms regulate MMP-9 activity, including gene transcription, proenzyme activation, and endogenous inhibitors such as tissue inhibitors of metalloproteinases (TIMPs).…”

Section: Introductionmentioning

confidence: 99%

Cordycepin inhibits TPA-induced matrix metalloproteinase-9 expression by suppressing the MAPK/AP-1 pathway in MCF-7 human breast cancer cells

Noh

Youn²,

Jung³

et al. 2009

Int J Mol Med

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Abstract. Matrix metalloproteinase-9 (MMP-9), which degrades the extracellular matrix (ECM), plays an important role in breast cancer cell invasion. NF-κB and AP-1 are known to induce MMP-9 expression. We investigated whether cordycepin, an NF-κB or AP-1 inhibitor, can modulate MMP-9 expression and cell invasion in MCF-7 cells. Toxicity of cordycepin was determined by 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. MMP-9 expression was determined by real-time PCR, Zymography, and Western blot analysis. AP-1 activation was assayed by electrophoretic mobility shift assay (EMSA). MAPK signaling was evaluated by Western blotting with specific p-ERK, and ERK, p-p38, p38, p-JNK, JNK antibodies. Cordycepin suppressed AP-1 activation, but not NF-κB activation in 12-O-tetradecanoylpho-bol-13-acetate (TPA)-treated MCF-7 cells. Cordycepin inhibits TPA-induced MMP-9 expression and cell invasion by suppressing AP-1 activation. Also, cordycepin suppressed the MAPK signaling pathway. Cordycepin is a potent inhibitor of TPA-induced MMP-9 expression and blocks strongly the ability of AP-1 activation via MAPK signaling pathway in MCF-7 cells.

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Section: Introductionmentioning

confidence: 99%

Cordycepin inhibits TPA-induced matrix metalloproteinase-9 expression by suppressing the MAPK/AP-1 pathway in MCF-7 human breast cancer cells

Noh

Youn²,

Jung³

et al. 2009

Int J Mol Med

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“…Furthermore, an increasing number of in vitro and in vivo studies have been conducted on the potential antimetastasis activity of fl avonoids in various tumor cells including human breast cancer. For example, quercetin and genistein have been shown to reduce human breast cancer cell invasion via down-regulation of MMP-1, -2, and -9 expression [24][25][26] . In an in vivo study, intraperitoneal administration of quercetin into syngeneic mice resulted in signifi cant inhibition of lung colonization in a dose-dependent manner [27] .…”

mentioning

confidence: 99%

Inhibition of MMP-3 activity and invasion of the MDA-MB-231 human invasive breast carcinoma cell line by bioflavonoids

et al. 2009

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IntroductionMetastatic invasion is the primary cause of patient mortality during breast cancer progression. For a transformed cell to metastasize to a distant site in the body, it must first lose adhesion, penetrate and invade the surrounding extracellular matrix (ECM), enter the vascular system, and adhere to distant organs [1] . The inhibition of invasion of cancer cells has been an important strategy in cancer treatment [2] . A crucial step in the invasive processes is the proteolytic degradation of the ECM and basal membranes [3] . Several studies have shown that among the enzymes responsible for ECM degradation, the matrix metalloproteinases (MMPs) appear to play a critical role [4][5][6] . MMPs are zinc-dependent endopeptidases, which collectively can degrade all constituents of the ECM. Based on their structure and substrate specificity, they can be divided into subgroups of collagenases, stromelysins, gelatinases, membrane-type MMPs and other MMPs [7] .Breast cancer is the major cause of malignancy-related deaths of women worldwide. In Thailand, breast cancer is the second most common cancer among women and its incidence is increasing [8] . Cancer invasion and metastasis are leading causes of morbidity and mortality in patients with breast cancer. Several studies have demonstrated that upregulation of MMP-1, -2, -3, -7, -9, -13, and -14 is associated with breast cancer cell invasion [9][10][11] .MMP-3, also designated stromelysin 1, is a member of the matrixin family, which plays a pivotal role in the degradation and remodeling of the ECM. MMP-3 degrades several components of the ECM, such as fi bronectin, laminin, collagen type IV [12][13][14] and proteoglycans, and is thought to play an important role in rheumatoid arthritis, osteoarthritis [15,16] , tumor cell invasion and metastasis [17] . Aim: Stromelysin 1 (matrix metalloproteinase 3; MMP-3) is an enzyme known to be involved in tumor invasion and metastasis. In this study, fl avonoids from vegetables and fruits, such as quercetin, kaempferol, genistein, genistin, and daidzein, were tested for their ability to modulate the secretion and activity of MMP-3 in the MDA-MB-231 breast cancer cell line. In addition, we investigated the in vitro effects of fl avonoids on MDA-MB-231 cell invasion. Methods: The toxic concentration range of fl avonoids was evaluated using the MTT assay. The ability of MDA-MB-231 cells to invade was evaluated using a modifi ed Boyden chamber system. The activity of MMP-3 was determined by casein zymography. The secretion of MMP-3 was evaluated using Western blotting, casein zymography and confi rmed by ELISA. Results: Some putative fl avonoids, ie, quercetin and kaempferol (fl avonols), signifi cantly inhibited the in vitro invasion of MDA-MB-231 cells in a concentration-dependent manner, with IC 50 values of 27 and 30 μmol/L, respectively. Quercetin and kaempferol also reduced MMP-3 activity in a dose-dependent manner, with IC 50 values in the range of 30 μmol/L and 45 μmol/L, respectively. None of the fl avonoids had a signif...

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“…The vasodilatation induced by EDHF has recently been considered to be resistant to both inhibitors of NO synthase and cyclooxygenase (Chen and Suzuki, 1990;Fukao et al, 1997;Félétou and Vanhoutte, 2002). Furthermore, the EDHFinduced relaxation is attenuated by high K ＋ or TEA (Campbell et al, 1996;Martinez-Orgado et al, 1999). In our laboratory, the quercetin-induced vasodilatation had less or no involvement in EDHF in rat aorta and mesenteric artery (unpublished data).…”

Section: Discussionmentioning

confidence: 67%

“…The activation of MLCK was abolished by PK-C (Hagiwara et al, 1988;Murthy et al, 2000). Furthermore, quercetin inhibits the phosphorylation of mitogen-activated protein kinases (MAPKs); extracellular signal-regulated kinase (ERK) 1/2, p38 MAPK, and c-jun amino-terminal kinase (JNK) in cultured aortic cells and phosphatidylinositol 3-kinase (PI3-kinase)/protein kinase B (Akt), leading to protection of proliferation and inflammation (Shin et al, 2004;Granado-Serrano et al, 2008;Lin et al, 2008;Kwon et al, 2009). Thus, quercetin produces the beneficial effects mediated through many cellular signaling pathways.…”

Section: Discussionmentioning

confidence: 99%

Possible Involvement of Ca2+ Activated K+ Channels, SK Channel, in the Quercetin-Induced Vasodilatation

Nishida

Satoh

2009

Korean J Physiol Pharmacol

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Effects of quercetin, a kind of flavonoids, on the vasodilating actions were investigated. Among the mechanisms for quercetin-induced vasodilatation in rat aorta, the involvement with the Ca 2＋ activated K ＋ (KCa) channel was examined. Pretreatment with NE (5 μM) or KCl (60 mM) was carried out and then, the modulation by quercetin of the constriction was examined using rat aorta ring strips (3 mm) at 36.5 o C. Quercetin (0.1 to 100 μM) relaxed the NE-induced vasoconstrictions in a concentrationdependent manner. NO synthesis (NOS) inhibitor, NG-monomethyl-L-arginine acetate (L-NMMA), at 100 μM reduced the quercetin (100 μM)-induced vasodilatation from 97.8±3.7% (n=10) to 78.0±11.6 % (n=5, p＜ 0.05). Another NOS inhibitor, L-NG-nitro arginine methyl ester (L-NAME), at 100 μM also had the similar effect. In the presence of both 100 μM L-NMMA and 10 μM indomethacin, the quercetin-induced vasodilatation was further attenuated by 100 μM tetraethylammonium (TEA, a KCa channel inhibitor). Also TEA decreased the quercetin-induced vasodilatation in endothelium-denuded rat aorta. Used other KCa channel inhibitors, the quercetin-induced vasodilatation was attenuated by 0.3 μM apamin (a SK channel inhibitor), but not by 30 nM charybdotoxin (a BK and IK channel inhibitor). Quercetin caused a concentration-dependent vasodilatation, due to the endotheliumdependent and -independent actions. Also quercetin contributes to the vasodilatation selectively with SK channel on smooth muscle.

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Quercetin inhibition of tumor invasion via suppressing PKC /ERK/AP-1-dependent matrix metalloproteinase-9 activation in breast carcinoma cells

Cited by 201 publications

References 42 publications

Cordycepin inhibits TPA-induced matrix metalloproteinase-9 expression by suppressing the MAPK/AP-1 pathway in MCF-7 human breast cancer cells

Cordycepin inhibits TPA-induced matrix metalloproteinase-9 expression by suppressing the MAPK/AP-1 pathway in MCF-7 human breast cancer cells

Inhibition of MMP-3 activity and invasion of the MDA-MB-231 human invasive breast carcinoma cell line by bioflavonoids

Possible Involvement of Ca2+ Activated K+ Channels, SK Channel, in the Quercetin-Induced Vasodilatation

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