Expression of the constitutively activated RelA/NF-κB in human astrocytic tumors and the in vitro implication in the regulation of urokinase-type plasminogen activator, migration, and invasion

Tsunoda, Keishi; Kitange, Gaspar J.; Anda, Takeo; Shabani, Hamisi K.; Kaminogo, Makio; Shibata, Shôbu; Nagata, Izumi

doi:10.1007/s10014-005-0186-1

Cited by 31 publications

(19 citation statements)

References 33 publications

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“…Data has shown that curcumin is able to suppress expression of MMP-1, MMP-3, MMP-9, and MMP-14 in GBM cell lines U87MG and U373MG via the common upstream AP-1 and MAP kinases [22, 23, 54]. Urokinase-type plasminogen activator (uPA) is a serine protease that starts a degradative cascade by converting extracellular plasminogen to plasmin and eventually degrades extracellular matrix collagen and activates other MMPs to aid in invasion [55]. Curcumin can prevent nuclear translocation of RelA/NF- κ B, which prevents upregulation of uPA [55].…”

Section: Mechanism and Preclinical Datamentioning

confidence: 99%

“…Urokinase-type plasminogen activator (uPA) is a serine protease that starts a degradative cascade by converting extracellular plasminogen to plasmin and eventually degrades extracellular matrix collagen and activates other MMPs to aid in invasion [55]. Curcumin can prevent nuclear translocation of RelA/NF- κ B, which prevents upregulation of uPA [55]. Curcumin has also been found to dramatically reduce MMP-9 in murine glioma cell lines Tu-2449, Tu-9648, and Tu-251 [49].…”

Section: Mechanism and Preclinical Datamentioning

confidence: 99%

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Therapeutic Potential of Curcumin for the Treatment of Brain Tumors

Klinger

Mittal

2016

Oxidative Medicine and Cellular Longevity

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Brain malignancies currently carry a poor prognosis despite the current multimodal standard of care that includes surgical resection and adjuvant chemotherapy and radiation. As new therapies are desperately needed, naturally occurring chemical compounds have been studied for their potential chemotherapeutic benefits and low toxicity profile. Curcumin, found in the rhizome of turmeric, has extensive therapeutic promise via its antioxidant, anti-inflammatory, and antiproliferative properties. Preclinical in vitro and in vivo data have shown it to be an effective treatment for brain tumors including glioblastoma multiforme. These effects are potentiated by curcumin's ability to induce G2/M cell cycle arrest, activation of apoptotic pathways, induction of autophagy, disruption of molecular signaling, inhibition of invasion, and metastasis and by increasing the efficacy of existing chemotherapeutics. Further, clinical data suggest that it has low toxicity in humans even at large doses. Curcumin is a promising nutraceutical compound that should be evaluated in clinical trials for the treatment of human brain tumors.

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Section: Mechanism and Preclinical Datamentioning

confidence: 99%

Section: Mechanism and Preclinical Datamentioning

confidence: 99%

Therapeutic Potential of Curcumin for the Treatment of Brain Tumors

Klinger

Mittal

2016

Oxidative Medicine and Cellular Longevity

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“…Since several studies have demonstrated that NF-κB is key in the transactivation of uPA and MMP9 (34)(35)(36), the present study investigated whether the activation of uPA and MMP9 may be attributed to NF-κB. As shown in Fig.…”

Section: Curcumin Inhibits P65 Nf-κb Dna Binding To the Upa And Mmp9 mentioning

confidence: 99%

Curcumin suppresses colon cancer cell invasion via AMPK-induced inhibition of NF–κB, uPA activator and MMP9

et al. 2016

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Abstract. Curcumin, an active nontoxic ingredient of turmeric, possesses potent anti-inflammatory, antioxidant and anti-cancer properties; however, the molecular mechanisms of curcumin are not fully understood. The transcription factor nuclear factor-κB (NF-κB) is key in cellular processes, and the expression/activation of urokinase-type plasminogen activator (uPA) and matrix metalloproteinase-9 (MMP9) are crucial for cell invasion. The present study investigated the hypothesis that curcumin inhibits colon cancer cell invasion by modulating NF-κB-mediated expression and activation of uPA and MMP9. Human colon cancer SW480 and LoVo cells were treated with various concentrations of curcumin. Curcumin was demonstrated to dose-dependently inhibit the adhesion and proliferation ability of LoVo and SW480 cells using Transwell and MTT assays, respectively. In addition, curcumin activated 5' AMP-activated protein kinase (AMPK) and suppressed p65 NF-κB phosphorylation, as shown by western blot analysis. Compound C, a potent AMPK inhibitor, abolished curcumin-induced inhibition of NF-κB, uPA and MMP9, suggesting that AMPK activation is responsible for curcumin-mediated NF-κB, uPA and MMP9 inhibition. The binding activity of NF-κB to DNA was examined and western blotting and quantitative polymerase reaction was performed to detect the effect of curcumin on the expression of uPA and MMP9. The present results revealed that curcumin significantly decreased the expression of uPA and MMP9 and NF-κB DNA binding activity. Furthermore, curcumin decreased the level of the p65 subunit of NF-κB binding to the promoter of the gene encoding uPA and MMP9, which suppressed transcriptional activation of uPA and MMP9. Overall, the present data suggest that curcumin inhibits colon cancer cell invasion via AMPK activation and subsequent inhibition of p65 NF-κB, uPA and MMP9. The therapeutic potential of curcumin for colon cancer metastasis required additional study.

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“…Because several studies have demonstrated that NF-kB might have a central role in the transactivation of uPA and uPAR (Killeen et al, 2009;Sliva et al, 2002;Tsunoda et al, 2005), we explored whether PKD2-and/or PKD3-dependent expression and activation of uPA could be attributed to upregulation of NF-kB signaling. As shown in Fig.…”

Section: Knockdown Of Pkd2 and Pkd3 Inhibits The Migration And Invasimentioning

confidence: 99%

PKD2 and PKD3 Promote Prostate Cancer Cell Invasion via uPA by Shifting Balance Between NF-κB and HDAC1

Zou

Zeng

et al. 2012

Journal of Cell Science

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SummaryAlthough protein kinase D3 (PKD3) has been shown to contribute to prostate cancer cell growth and survival, the role of PKD in prostate cancer cell motility remains unclear. Here, we show that PKD2 and PKD3 promote nuclear factor kappa B (NF-kB) signaling and urokinase-type plasminogen activator (uPA) expression/activation, which are crucial for prostate cancer cell invasion. Silencing of endogenous PKD2 and/or PKD3 markedly decreased prostate cancer cell migration and invasion, reduced uPA and uPA receptor (uPAR) expression and increased plasminogen activator inhibitor-2 (PAI-2) expression. These results were further substantiated by the finding that PKD2 and PKD3 promoted the activity of uPA and matrix metalloproteinase 9 (MMP9). Furthermore, depletion of PKD2 and/or PKD3 decreased the level of binding of the p65 subunit of NF-kB to the promoter of the gene encoding uPA (PLAU), suppressing transcriptional activation of uPA. Endogenous PKD2 and PKD3 interacted with inhibitor of NF-kB (IkB) kinase b (IKKb); PKD2 mainly regulated the phosphorylated IKK (pIKK)-phosphorylated IkB (pIkB)-IkB degradation cascade, p65 nuclear translocation, and phosphorylation of Ser276 on p65, whereas PKD3 was responsible for the phosphorylation of Ser536 on p65. Conversely, inhibition of uPA transactivation by PKD3 silencing was rescued by constitutive Ser536 p65 phosphorylation, and reduced tumor cell invasion resulting from PKD2 or PKD3 silencing was rescued by ectopic expression of p65. Interestingly, PKD3 interacted with histone deacetylase 1 (HDAC1), suppressing HDAC1 expression and decreasing its binding to the uPA promoter. Moreover, depletion of HDAC1 resulted in recovery of uPA transactivation in PKD3-knockdown cells. Taken together, these data suggest that PKD2 and PKD3 coordinate to promote prostate cancer cell invasion through p65 NF-kB-and HDAC1-mediated expression and activation of uPA.

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Expression of the constitutively activated RelA/NF-κB in human astrocytic tumors and the in vitro implication in the regulation of urokinase-type plasminogen activator, migration, and invasion

Cited by 31 publications

References 33 publications

Therapeutic Potential of Curcumin for the Treatment of Brain Tumors

Therapeutic Potential of Curcumin for the Treatment of Brain Tumors

Curcumin suppresses colon cancer cell invasion via AMPK-induced inhibition of NF–κB, uPA activator and MMP9

PKD2 and PKD3 Promote Prostate Cancer Cell Invasion via uPA by Shifting Balance Between NF-κB and HDAC1

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