UNIPROT:P05412 - FACTA Search

Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P05412 (c-Jun)
11,453 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Acacetin (5,7-dihydroxy-4'-methoxyflavone), a flavonoid compound, has anti-peroxidative and anti-inflammatory effects. The effect of acacetin on antimetastasis in human prostate cancer DU-145 cells was investigated. First, the result demonstrated acacetin could exhibit an inhibitory effect on the abilities of the adhesion, invasion, and migration by cell-matrix adhesion assay, wound-healing assay, and Boyden chamber assay. Data also showed acacetin could inhibit the phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK) involved in the downregulation of the expressions of matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), and urokinase-type plasminogen activator (u-PA) at both the protein and mRNA levels. Next, acacetin significantly decreased the nuclear levels of nuclear factor kappa B (NF-kappaB), c-Fos, and c-Jun. Also, the treatment with acacetin to DU145 cells also leads to a dose-dependent inhibition on the binding ability of NF-kappaB and activator protein-1 (AP-1). Furthermore, the treatment of inhibitors specific for p38 MAPK (SB203580) to DU145 cells could cause reduced expressions of MMP-2, MMP-9, and u-PA. These results showed acacetin could inhibit the invasion and migration abilities of DU145 cells by reducing MMP-2, MMP-9, and u-PA expressions through suppressing p38 MAPK signaling pathway and inhibiting NF-kappaB- or AP-1-binding activity. These findings proved acacetin might be offered further application as an antimetastatic agent.
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PMID:Acacetin, a flavonoid, inhibits the invasion and migration of human prostate cancer DU145 cells via inactivation of the p38 MAPK signaling pathway. 1969 51

This study is the first to investigate the antimetastatic effect of fisetin in human lung adenocarcinoma A549 cells. Fisetin exhibited an inhibitory effect on the abilities of adhesion, migration, and invasion via inhibiting the phosphorylation of extracellular signal-regulated kinase 1 and 2 (ERK1/2) and downregulating the expressions of matrix metalloproteinase-2 (MMP-2) and urokinase-type plasminogen activator (u-PA) at both the protein and mRNA levels in A549 cells. Next, fisetin significantly decreased the nuclear levels of nuclear factor kappa B (NF-kappaB), c-Fos, and c-Jun. Also, treating A549 cells with fisetin also leads to a concentration-dependent inhibition on the binding abilities of NF-kappaB and activator protein-1 (AP-1). Furthermore, reduction of ERK1/2 phosphorylation by ERK small interfering RNA (ERK siRNA) potentiated the effect of fisetin, supporting the inhibition of ERK1/2 being beneficial to antimetastasis. Finally, the transient transfection of ERK siRNA significantly downregulated the expressions of MMP-2 and u-PA concomitantly with a marked inhibition of cell invasion and migration. Taken together, these results implied a critical role for ERK1/2 inhibition in fisetin-reduced invasion and migration of A549 cells.
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PMID:Involvement of the ERK signaling pathway in fisetin reduces invasion and migration in the human lung cancer cell line A549. 1972 38

We investigated whether oral administration of curcumin suppressed type II collagen-induced arthritis (CIA) in mice and its effect and mechanism on matrix metalloproteinase (MMP)-1 and MMP-3 production in CIA mice, RA fibroblast-like synoviocytes (FLS), and chondrocytes. CIA in mice was suppressed by oral administration of curcumin in a dose-dependent manner. Macroscopic observations were confirmed by histological examinations. Histological changes including infiltration of immune cells, synovial hyperplasia, cartilage destruction, and bone erosion in the hind paw sections were extensively suppressed by curcumin. The histological scores were consistent with clinical arthritis indexes. Production of MMP-1 and MMP-3 were inhibited by curcumin in CIA hind paw sections and tumor necrosis factor (TNF)-alpha-stimulated FLS and chondrocytes in a dose-dependent manner. As for the mechanism, curcumin inhibited activating phosphorylation of protein kinase Cdelta (PKCdelta) in CIA, FLS, and chondrocytes. Curcumin also suppressed the JNK and c-Jun activation in those cells. This study suggests that the suppression of MMP-1 and MMP-3 production by curcumin in CIA is mediated through the inhibition of PKCdelta and the JNK/c-Jun signaling pathway.
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PMID:Oral administration of curcumin suppresses production of matrix metalloproteinase (MMP)-1 and MMP-3 to ameliorate collagen-induced arthritis: inhibition of the PKCdelta/JNK/c-Jun pathway. 1976 44

This study first investigates the anti-metastatic effect of plumbagin (5-hydroxy-2-methyl-1,4-naphthoquinone) on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced MMPs and u-PA expressions in human lung cancer cells, A549. First, the result demonstrated plumbagin could inhibit TPA induced the abilities of the adhesion, invasion, and migration by cell-matrix adhesion assay and Boyden chamber assay. Data also showed plumbagin could inhibit the activation of extracellular signal-regulated kinase 1 and 2 (ERK1/2) involved in the down-regulating enzyme activities, protein and messenger RNA levels of matrix metalloproteinase-2 (MMP-2), and urokinase-type plasminogen activator (u-PA) induced by TPA. Next, plumbagin also strongly inhibited TPA-induced phosphorylation and degradation of inhibitor of kappaBalpha (IkappaBalpha), and the nuclear levels of nuclear factor kappa B (NF-kappaB), c-Fos, and c-Jun. Also, a dose-dependent inhibition on the binding abilities of NF-kappaB and activator protein-1 (AP-1) by plumbagin treatment was further observed. Further, the treatment of specific inhibitor for ERK (U0126) to A549 cells could inhibit TPA-induced MMP-2 and u-PA expressions along with an inhibition on cell invasion and migration. Presented data reveals that plumbagin is a novel, effective, anti-metastatic agent that functions by down-regulating MMP-2 and u-PA gene expressions.
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PMID:Plumbagin inhibits TPA-induced MMP-2 and u-PA expressions by reducing binding activities of NF-kappaB and AP-1 via ERK signaling pathway in A549 human lung cancer cells. 1976 35

S-Adenosylhomocysteine (SAH) is a risk factor for many diseases, including tumor progression and neurodegenerative disease. In this study, we examined the hypothesis that SAH may indirectly enhance the invasion of C6 glioma cells by induction of matrix metalloproteinase-2 (MMP-2) secreted from the murine microglia BV2 cells. We obtained conditioned medium (CM) by incubating BV2 cells with SAH (1-50nM) for 24 h. We found that the SAH-containing CM (SAH-BV2-CM) strongly enhanced the invasiveness of C6 glioma cells and that this effect increased with increasing concentrations of SAH in the SAH-BV2-CM. The effect of CM could be attributed to its MMP-2 activity, as a result of increased protein and messenger RNA expression of MMP-2 in BV2 cells induced by SAH. In BV2 cells treated with SAH, the binding abilities of nuclear factor-kappa B (NF-kappaB) and stimulatory protein-1 (Sp1) to the MMP-2 promoter were increased, whereas the level of NF-kappaB inhibitor was decreased. In addition, SAH significantly increased the phosphorylation of extracellular signal-regulated kinase (ERK) and phosphatidylinositol-3-kinase/serine/threonine protein kinase (or protein kinase B) (PI3K/Akt) proteins but did not affect that of c-Jun NH2-terminal kinase or p38. Pretreatment of BV2 cells with an inhibitor specific for ERK (U0126) markedly abated the expression of ERK and MMP-2. Furthermore, SAH significantly and dose dependently decreased tissue inhibitor of metalloproteinase-2 (TIMP-2) in BV2 cells. Thus, SAH may induce the invasiveness of C6 glioma cells by decreased TIMP-2 expression and increased MMP-2 expression in BV2 cells. The latter effect is likely mediated through the ERK and PI3K/Akt pathways, with increased binding activities of NF-kappaB and Sp1 to the MMP-2 gene promoter.
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PMID:S-Adenosylhomocysteine promotes the invasion of C6 glioma cells via increased secretion of matrix metalloproteinase-2 in murine microglial BV2 cells. 1977 Apr 85

The thorns of Gleditsia sinensis have traditionally been used in the treatment of several diseases, which includes their use as anti-tumor agents, but there has been no scientific evidence of this anti-tumor effect. However, the present study has identified a novel mechanism for the anti-tumor effect of Gleditsia sinensis thorns in the treatment of colon cancer. Treatment with the ethanol extract of Gleditsia sinensis thorns (EEGS) resulted in significant growth inhibition together with G2/M-phase cell cycle arrest at a dose of 600 microg/ml (IC50) in HCT116 cells. In addition, treatment with EEGS induced p27 expression and down-regulated expression of cyclins and cyclin-dependent kinases. Moreover, EEGS treatment induced phosphorylation of extracellular signal-regulated kinases (ERK), p38 MAP kinase and JNK (c-Jun N-terminal kinases). Among the pathways examined, only PD98059 (ERK-specific inhibitor) abolished EEGS-dependent p27 expression. Similarly, suppression of ERK function reversed EEGS-mediated cell proliferation inhibition and decreased cell cycle proteins. In addition, tumor necrosis factor-alpha (TNF-alpha)-induced matrix metalloproteinase-9 (MMP-9) expression was inhibited by EEGS treatment via decreased transcriptional activity of both activator protein-1 (AP-1) and nuclear factor-kappaB. Finally, EEGS treatment significantly reduced tumor sizes in HCT116 cell-xenografted tumor tissues, which was associated with the changed levels of ERK phosphorylation, p27 and MMP-9 expression. Overall, these results have identified a novel molecular mechanism for EEGS in the treatment of colon cancer and might provide a theoretical basis for the potential therapeutic use of EEGS in the treatment of malignancies.
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PMID:Inhibitory effects of the ethanol extract of Gleditsia sinensis thorns on human colon cancer HCT116 cells in vitro and in vivo. 1988 6

MMP-9, a member of the matrix metalloproteinase family that degrades collagen IV and processes chemokines and cytokines, participates in epidermal remodeling in response to stress and injury. Limited activity of MMP-9 is essential while excessive activity is deleterious to the healing process. Tumor necrosis factor (TNFalpha), a key mediator of cutaneous inflammation, is a powerful inducer of MMP-9. Calcitriol, the hormonally active vitamin D metabolite, and its analogs are known to attenuate epidermal inflammation. We aimed to examine the modulation of MMP-9 by calcitriol in TNFalpha-treated keratinocytes. The immortalized HaCaT keratinocytes were treated with TNFalpha in the absence of exogenous growth factors or active ingredients. MMP-9 production was quantified by gelatin zymography and real-time RT-PCR. Activation of signaling cascades was assessed by western blot analysis and DNA-binding activity of transcription factors was determined by EMSA. Exposure to TNFalpha markedly increased the protein and mRNA levels of MMP-9, while pretreatment with calcitriol dose dependently reduced this effect. Employing specific inhibitors we established that the induction of MMP-9 by TNFalpha was dependent on the activity of the epidermal growth factor receptor, c-Jun-N-terminal kinase (JNK), NFkappaB and extracellular signal-regulated kinase-1/2. The effect of calcitriol was associated with inhibition of JNK activation and reduction of DNA-binding activities of the transcription factors activator protein-1 (AP-1) and NFkappaB following treatment with TNFalpha. By down-regulating MMP-9 levels active vitamin D derivatives may attenuate deleterious effects due to excessive TNFalpha-induced proteolytic activity associated with cutaneous inflammation.
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PMID:Upregulation of MMP-9 production by TNFalpha in keratinocytes and its attenuation by vitamin D. 2002 Apr 46

Benzyl isothiocyanate (BITC), a component of dietary cruciferous vegetables, has antioxidant and anticancer properties. In this study, we show for the first time the antimetastatic effects of BITC in human colon cancer HT29 cells. BITC had an inhibitory effect on cell migration and invasion. Protein levels of matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), and urokinase-plasminogen activator (u-PA) were reduced by BITC in a concentration-dependent manner. BITC also exerted an inhibitory effect on phosphorylation of c-Jun N-terminal kinase 1 and 2 (JNK1/2), extracellular signal-regulated kinases 1 and 2 (ERK1/2), phosphatidylinositol 3-kinase (PI3K) and protein kinase C (PKC) that are upstream of nuclear factor kappa B (NF-kappaB). BITC inhibited DNA binding activity of NF-kappaB. Moreover, BITC decreased the levels of c-Fos, c-Jun, Ras, FAK, PI3K and GRB2 in HT29 cells. Reductions in the enzyme activity, protein and mRNA (mRNA) levels of MMP-2 were observed in BITC-treated HT29 cells. BITC also inhibited mRNA levels of MMP-2, -7, and -9 in HT29 cells. Results from zymography showed that BITC treatment decreased MMP-2 expression in a concentration-dependent manner. BITC inhibited PKCdelta activity in HT29 cells. Furthermore, inhibitors specific for JNK (SP600125) reduced expression of MMP-2, MMP-9, and u-PA. These results demonstrated that BITC could alter HT29 cell metastasis by reduction of MMP-2, MMP-9, and u-PA expression through the suppression of a PKC, MAPK signaling pathway and inhibition of NF-kappaB levels. These findings suggest that BITC has potential as an antimetastatic agent.
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PMID:Benzyl isothiocyanate (BITC) inhibits migration and invasion of human colon cancer HT29 cells by inhibiting matrix metalloproteinase-2/-9 and urokinase plasminogen (uPA) through PKC and MAPK signaling pathway. 2013 87

Hesperidin (HES) has been reported to exhibit anti-invasive and antimetastatic activities by suppressing the enzymatic activity of matrix metalloproteinase-9 (MMP-9). However, the underlying mechanism of anti-invasive activity remains unclear so far. First, we suggest that the expression of MMP-9 by TPA involves phosphorylation of IKK, p38, and PKC in hepG2. We also demonstrate that hesperidin reduced 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced cell invasion and inhibited the secreted and cytosolic MMP-9 forms in HepG2 cells. Hesperidin significantly suppressed the TPA-induced the mRNA level of MMP-9. Hesperidin suppressed MMP-9 transcription by inhibiting nuclear factor-kappaB (NF-kappaB) and Activator protein 1 (AP-1) activity. Hesperidin suppressed TPA-stimulated NF-kappaB translocation into the nucleus through IkappaB inhibitory signaling pathways and also inhibited TPA-induced AP-1 activity by the inhibitory phosphorylation of p38 kinase and c-Jun N-terminal kinase (JNK) signaling pathways. In conclusion, Hesperidin might be a potent antiinvasive agent that suppresses the MMP-9 enzymatic activity via NF-kappaB an AP-1 signaling pathway.
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PMID:The inhibitory effect of hesperidin on tumor cell invasiveness occurs via suppression of activator protein 1 and nuclear factor-kappaB in human hepatocellular carcinoma cells. 2013 77

Cardiac fibroblasts play important roles during the cardiac remodeling through the secretion of matrix metalloproteinase (MMP)-9. Inflammatory cytokine, interleukin (IL)-1beta induces MMP-9 secretion in cultured cardiac fibroblasts. Angiotensin II is well known to play pivotal roles in cardiac remodeling, but the effect of angiotensin II on MMP-9 secretion in cardiac fibroblasts has not been fully clarified. In the present study, we investigated the effect of angiotensin II on basal and IL-1beta-induced MMP-9 secretion in adult rat cardiac fibroblasts. MMP-9 protein secreted into culture medium, and phosphorylation of nuclear factor (NF)-kappaB, c-Jun NH(2)-terminal kinase (JNK), and extracellular signal-regulated kinase (ERK) in cell lysates were measured by Western blotting. Angiotensin II (1 nM, 24 hr) alone-treatment did not induce MMP-9 secretion. However, angiotensin II significantly enhanced IL-1beta (4 ng/ml, 24 hr)-induced MMP-9 secretion. Telmisartan (10 nM), an angiotensin II type 1 receptor (AT1R) antagonist, significantly suppressed the enhancement of IL-1beta-induced MMP-9 secretion by angiotensin II, whereas PD123319 (10 nM), an angiotensin II type 2 receptor antagonist, was ineffective. IL-1beta (4 ng/ml, 10 min) induced phosphorylation of NF-kappaB, JNK, and ERK. Angiotensin II augmented the IL-1beta-induced phosphorylation of ERK but not NF-kappaB and JNK. PD98059 (50 microM), a selective inhibitor of ERK pathway, inhibited the angiotensin II enhancement of IL-1beta-induced MMP-9 secretion. These results suggest that angiotensin II enhances IL-1beta-induced MMP-9 secretion through the augmentation of ERK phosphorylation via AT1R in adult rat cardiac fibroblasts.
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PMID:Angiotensin II enhances interleukin-1 beta-induced MMP-9 secretion in adult rat cardiac fibroblasts. 2014 75

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