Adenosine dialdehyde suppresses MMP-9-mediated invasion of cancer cells by blocking the Ras/Raf-1/ERK/AP-1 signaling pathway

Kim, Ji Hye; Kim, Jong Heon; Kim, Seung Cheol; Yi, Young-Su; Yang, Woo Seok; Yang, Yanyan; Kim, Han Gyung; Lee, Jae Yong; Kim, Kyung Hee; Yoo, Byong Chul; Hong, Sungyoul; Cho, Jae Youl

doi:10.1016/j.bcp.2013.08.022

Cited by 42 publications

(39 citation statements)

References 62 publications

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“…of Dipyridamole on the Phosphorylation of MEK and ERK Previous studies have shown that extracellular adenosine and intracellular Sadenosylhomocysteine levels affect the activation of the MEK/ERK signalling pathway (21,22). The results from immunoblot showed that treatment with homocysteine and adenosine reduced the expressions of p-MEK1/2 and p-ERK1/2 (Fig 6A).…”

Section: Influencementioning

confidence: 77%

“…In terms of MEK/ERK signalling pathway, the effects of extracellular adenosine and intracellular Sadenosylhomocysteine concentrations on its activations have been previously reported. Intracellular S-adenosylhomocysteine accumulation inhibited the activities of isoprenylcysteine carboxyl methyltransferase and repressed the carboxyl methylation of Ras and its membrane translocation, leading to the inhibition of the cRaf/MEK/ERK signalling pathway (21). Meanwhile, the increase in extracellular adenosine concentration could lead to adenosine receptor activation.…”

Section: Discussionmentioning

confidence: 99%

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Nucleoside Transport Inhibition by Dipyridamole Prevents Angiogenesis Impairment by Homocysteine and Adenosine

et al. 2015

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-Purpose. Adenosine plays an important role in the pathogenesis of homocysteine-associated vascular complications. Methods: This study examined the effects of dipyridamole, an inhibitor for nucleoside transport, on impaired angiogenic processes caused by homocysteine and adenosine in human cardiovascular endothelial cell line (EAhy926). Results: The results showed that dipyridamole restored the extracellular adenosine and intracellular S-adenosylhomocysteine concentrations disrupted by the combination of homocysteine and adenosine. Dipyridamole also ameliorated the impaired proliferation, migration and formation of capillary-like tubes of EAhy926 cells caused by the combination of homocysteine and adenosine. Mechanism analysis revealed that dipyridamole induced the phosphorylation of mitogen-activated protein kinase kinase (MEK) and extracellular signal-regulated kinases (ERK) and its effect on cell growth was attenuated by the MEK inhibitor, U0126. Conclusion: Dipyridamole protected against impaired angiogenesis caused by homocysteine and adenosine, at least in part, by activating the MEK/ERK signalling pathway, and this could be associated with its effects in suppressing intracellular S-adenosylhomocysteine accumulation. Novelty of the Work: This is the first paper showing that nucleoside transport inhibition by dipyridamole reduced impaired angiogenic process caused by homocysteine and adenosine.

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Section: Influencementioning

confidence: 77%

Section: Discussionmentioning

confidence: 99%

Nucleoside Transport Inhibition by Dipyridamole Prevents Angiogenesis Impairment by Homocysteine and Adenosine

et al. 2015

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“…To test the effect of lancemaside A on the plastic adherence of cells, a wound healing assay was performed as reported previously [36]. Monolayers of RAW264.7 cells were grown to 90% confluence in 6-well plates.…”

Section: Methodsmentioning

confidence: 99%

Lancemaside A fromCodonopsis lanceolataModulates the Inflammatory Responses Mediated by Monocytes and Macrophages

Kim

Yang

Kim

et al. 2014

Mediators of Inflammation

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In this study, we aimed to examine the cellular and molecular mechanisms of lancemaside A from Codonopsis lanceolata (Campanulaceae) in the inflammatory responses of monocytes (U937 cells) and macrophages (RAW264.7 cells). Lancemaside A significantly suppressed the inflammatory functions of lipopolysaccharide- (LPS-) treated RAW264.7 cells by suppressing the production of nitric oxide (NO), the expression of the NO-producing enzyme inducible NO synthase (iNOS), the upregulation of the costimulatory molecule CD80, and the morphological changes induced by LPS exposure. In addition, lancemaside A diminished the phagocytic activity of RAW264.7 cells and boosted the neutralizing capacity of these cells when treated with the radical generator sodium nitroprusside (SNP). Interestingly, lancemaside A strongly blocked the adhesion activity of RAW264.7 cells to plastic culture plates, inhibited the cell-cell and cell-fibronectin (FN) adhesion of U937 cells that was triggered by treatment with an anti-β1-integrin (CD29) antibody and immobilized FN, respectively. By evaluating the activation of various intracellular signaling pathways and the levels of related nuclear transcription factors, lancemaside A was found to block the activation of inhibitor of κB kinase (IKK) and p65/nuclear factor- (NF-) κB. Taken together, our findings strongly suggest that the anti-inflammatory function of lancemaside A is the result of its strong antioxidative and IKK/NF-κB inhibitory activities.

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“…A previous study demonstrated that polymerization of globular actin to F-actin is a key process in the inflammatory response (Du et al, 2012). Another study reported that disruption of the F-actin cytoskeleton structure induced Src deactivation by suppressing the formation of a signaling complex consisting of Src and p85/PI3K (Kim et al, 2013), suggesting that the inflammatory signals induce the formation of F-actin, and the F-actin subsequently activates Src, leading to the induction of the inflammatory signal transduction cascades in macrophages. To examine this, RAW264.7 cells were stimulated by LPS, and F-actin formation was evaluated.…”

Section: Discussionmentioning

confidence: 99%

MyD88-Syk axis is a critical determinant for inflammatory response in macrophages

Kim

Yang

et al. 2019

Preprint

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32 Inflammation, a vital immune response to infection and injury, is mediated by macrophage 33 activation. Spleen tyrosine kinase (Syk) and myeloid differentiation primary response 88 34 (MyD88) regulate the inflammatory response in macrophages, however, their roles and the 35 underlying mechanisms are still largely unknown. In this study, the role of the MyD88-Syk 36 axis and the mechanism by which Syk and MyD88 cooperate during macrophage-mediated 37 inflammatory responses were investigated. Inhibition of Syk or MyD88 decreased both 38 generation of reactive oxygen species (ROS)/reactive nitrogen species (RNS) and consequent 39 ROS/RNS-induced phagocytic activity in lipopolysaccharide (LPS)-stimulated RAW264.7 40 cells. Syk inhibition downregulated expression of ROS/RNS-generating enzymes by inhibiting 41 the nuclear factor-kappa B (NF-B) signaling pathway and phagocytic activity by suppressing 42 suppressor of cytokine signaling 1 (SOCS1) via its nitration in the LPS-stimulated RAW264.7 43 cells. Inhibition of ROS/RNS generation suppressed SOCS1 nitration, leading to a decrease in 44 the phagocytic activity of macrophages. Syk was activated by the interaction with MyD88, and 45 the tyrosine 58 residue (Y58) in the hemi-immunoreceptor tyrosine-based activation motif 46 (ITAM) of MyD88 was critical for their interaction and the consequent activation of Syk in 47 macrophages. Src activated MyD88 by phosphorylation at Y58 via the Src kinase domain. 48 Moreover, LPS-induced formation of filamentous actin (F-actin) and Ras-related C3 botulinum 49 toxin substrate 1 (Rac1) activation induced Src activation. Conclusively, these results suggest 50 that the MyD88-Syk axis plays a pivotal role in macrophage-mediated inflammatory responses 51 by inducing ROS/RNS generation and phagocytic activity via activation of Src and its upstream 52 stimulators, F-actin and Rac1. 53 54

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Adenosine dialdehyde suppresses MMP-9-mediated invasion of cancer cells by blocking the Ras/Raf-1/ERK/AP-1 signaling pathway

Cited by 42 publications

References 62 publications

Nucleoside Transport Inhibition by Dipyridamole Prevents Angiogenesis Impairment by Homocysteine and Adenosine

Nucleoside Transport Inhibition by Dipyridamole Prevents Angiogenesis Impairment by Homocysteine and Adenosine

Lancemaside A fromCodonopsis lanceolataModulates the Inflammatory Responses Mediated by Monocytes and Macrophages

MyD88-Syk axis is a critical determinant for inflammatory response in macrophages

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