Suppression of matrix metalloproteinase‐9 by 4‐methylumbelliferone

Nakamura, Rika; Kuwabara, Hiroko; Yoneda, Masahiko; Yoshihara, Shuichi; Ishikawa, Takashi; Miura, Tomisato; Nozaka, Hiroyuki; Nanashima, Naoki; Sato, Tatsusuke; Nakamura, Toshiya

doi:10.1016/j.cellbi.2007.03.016

Cited by 15 publications

(15 citation statements)

References 24 publications

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“…For example, 4-MU induces the expression of MT1-MMP mRNA, resulting in activation of MMP2 in human skin fibroblasts (67), but in human lymphoma cell lines, 4-MU decreased the level of mRNA for MMP9 (68). In primary human aortic smooth muscle cells 4-MU did not modify the activity of MMP2 but did cause a decrease in cellular migration, migration that could be rescued with the addition of HA (63).…”

Section: Discussionmentioning

confidence: 98%

“…Whether this inhibition was dependent on HA inhibition or a direct effect remains unknown. Nakamura et al (68) reported that 4-MU inhibited MMP9 in a human lymphoma cell line as well as other cultured human carcinoma cells, an inhibition that could not be mimicked by treatment of the cells with hyaluronidase. Given that elevated HA accumulation is often positively correlated with tumor growth and aggressiveness (31,69), it is not surprising that 4-MU would provide inhibitory effects on tumor cell migration, invasion, or cell proliferation by way of blocking HA production.…”

Section: Discussionmentioning

confidence: 99%

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4-Methylumbelliferone Diminishes Catabolically Activated Articular Chondrocytes and Cartilage Explants via a Mechanism Independent of Hyaluronan Inhibition

Ishizuka

Askew

Ishizuka

et al. 2016

Journal of Biological Chemistry

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Depletion of the cartilage proteoglycan aggrecan is one of the earliest events that occurs in association with osteoarthritis. This loss is often accompanied by a coordinate loss in another glycosaminoglycan, hyaluronan. Chondrocytes experimentally depleted of cell-associated hyaluronan respond by switching to a pro-catabolic metabolism that includes enhanced production of endogenous inflammatory mediators and increased synthesis of matrix metalloproteinases. Hyaluronan turnover is also increased. Together, such a response provides for possible establishment of a self-perpetuating spiral of events that maintains or prolongs the pro-catabolic state. Chondrocytes or cartilage can also be activated by treatment with pro-inflammatory cytokines and mediators such as IL-1␤, TNF␣, LPS, fibronectin fragments, and hyaluronan oligosaccharides. To determine the mechanism of chondrocyte activation due to hyaluronan loss, a depletion method was required that did not include degrading the hyaluronan. In recent years, several laboratories have used the coumarin derivative, 4-methylumbelliferone, as a potent inhibitor of hyaluronan biosynthesis, due in part to its ability to sequester intracellular UDP-glucuronic acid and inhibition of hyaluronan synthase transcription. However, contrary to our expectation, although 4-methylumbelliferone was indeed an inhibitor of hyaluronan biosynthesis, this depletion did not give rise to an activation of chondrocytes or cartilage. Rather, 4-methylumbelliferone directly and selectively blocked gene products associated with the pro-catabolic metabolic state of chondrocytes and did so through a mechanism preceding and independent of hyaluronan inhibition. These data suggest that 4-methylumbelliferone has additional useful applications to block pro-inflammatory cell activation events but complicates how it is used for defining functions related to hyaluronan.The pronounced loss of aggrecan from articular cartilage is an early critical event associated with osteoarthritis (OA) 2 (1, 2). Aggrecan turnover within the extracellular matrix occurs due to the enhanced activity of endoproteinases such as a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) 4 (3, 4) and 5 (5, 6) as well as other matrix metalloproteinases (MMPs) (7)(8)(9)(10)(11). In addition to aggrecan, a significant loss of hyaluronan (HA) is also observed in human OA cartilage as compared with normal human cartilage (12,13). A marked depletion of HA was also observed in articular cartilage damaged experimentally, such as in the anterior cruciate ligament transection model of OA (14) and a reduced-loading, splint immobilization model (15) in dogs. In our studies, cultured explants of human articular cartilage treated with IL-1␣ displayed a loss of HA within the superficial and upper middle layers of cartilage, the same layers in which aggrecan loss occurred (16). Other studies on cytokine-stimulated cartilage explants suggested that HA is lost from the cartilage (17,18), and other studies revealed that the HA is lost...

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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

4-Methylumbelliferone Diminishes Catabolically Activated Articular Chondrocytes and Cartilage Explants via a Mechanism Independent of Hyaluronan Inhibition

Ishizuka

Askew

Ishizuka

et al. 2016

Journal of Biological Chemistry

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“…MMP-9 is produced by neutrophil granulocytes, macrophages, malignant cells and capillary endothelial cells (27). MMP-9 can promote cancer cells to have infiltration invasion through the degradation and destruction of the basilar membrane or new vessels to enhance cancer growth and dissemination (28).…”

Section: Discussionmentioning

confidence: 99%

Andrographolide suppresses proliferation of human colon cancer SW620 cells through the TLR4/NF-κB/MMP-9 signaling pathway

Zhang

Zhao

et al. 2017

Oncology Letters

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Abstract. Modern pharmacological research has revealed that andrographolide has various functions, including anti-bacterial, anti-inflammatory and anti-viral effects, immunoregulation, treating cardiovascular and cerebrovascular diseases, and prevention and treatment of alcoholic liver injury. The present study investigated whether andrographolide suppresses the proliferation of human colon cancer cell through the Toll-like receptor 4 (TLR4)/nuclear factor (NF)-κB/matrix metalloproteinase-9 (MMP-9) signaling pathway. The MTT assay and lactate dehydrogenase assay were used to evaluate the anticancer effects of andrographolide on cell proliferation and cytotoxicity in human colon cancer SW620 cells.Flow cytometry was used to analyze the anticancer effects of andrographolide on apoptosis by Annexin V-fluorescein isothiocyanate/propidium iodide kit. The effects of andrographolide on the activity of caspase-3/9 were measured using ELISA. Western blot analysis was also used to analyze the protein expression of TLR4, myeloid differentiation primary response gene 88 (MyD88), NF-κB-p65 and MMP-9. In the present study, it was found that andrographolide suppressed the cell proliferation, augmented cytotoxicity, evoked cell apoptosis and activated caspase-3/9 activities in human colon cancer SW620 cells. The results revealed that the anti-proliferation effects of andrographolide on the SW620 cells was associated with the inhibition of TLR4, MyD88, NF-κB-p65 and MMP-9 signaling activation. The results suggest that andrographolide is a promising drug for treatment of human colon cancer via suppression of the TLR4/NF-κB/MMP-9 signaling pathway.

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“…In breast cancer in transgenic mice, HA overproduction accelerates tumor angiogenesis through stromal reactions, most notably in the presence of versican [24]. On the other hand, the HAS suppressor, 4-methylumbelliferone (MU), suppresses cell adhesion, locomotion, and matrix metalloproteinase (MMP)-9 and N-cadherin expression, and inhibits tumor metastasis [25][26][27]. HA is composed of high and low molecular weight forms that have been shown to have opposite functions.…”

Section: Hyaluronan and Receptors For Hyaluronan-mediated Motilitymentioning

confidence: 99%

Expressional Alterations of Versican, Hyaluronan and Microfibril Associated Proteins in the Cancer Microenvironment

Kuwabara¹,

Yoneda²,

Isogai³

2013

Carcinogenesis

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Suppression of matrix metalloproteinase‐9 by 4‐methylumbelliferone

Cited by 15 publications

References 24 publications

4-Methylumbelliferone Diminishes Catabolically Activated Articular Chondrocytes and Cartilage Explants via a Mechanism Independent of Hyaluronan Inhibition

4-Methylumbelliferone Diminishes Catabolically Activated Articular Chondrocytes and Cartilage Explants via a Mechanism Independent of Hyaluronan Inhibition

Andrographolide suppresses proliferation of human colon cancer SW620 cells through the TLR4/NF-κB/MMP-9 signaling pathway

Expressional Alterations of Versican, Hyaluronan and Microfibril Associated Proteins in the Cancer Microenvironment

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