Insidious role of nitric oxide in migration/invasion of colon cancer cells by upregulating MMP-2/9 via activation of cGMP-PKG-ERK signaling pathways

Babykutty, Suboj; Suboj, Priya; Srinivas, Priya; Nair, Asha S.; Chandramohan, K; Gopala, Srinivas

doi:10.1007/s10585-012-9464-6

Cited by 79 publications

(59 citation statements)

References 69 publications

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“…Inhibiting cancer cell metastasis is one of the important steps for cancer therapy and research (5). Numerous evidence have shown that multiple factors involved in tumor metastasis, such as the activation of PI3K/Akt pathway (6), matrix metalloproteinases (MMPs)-enzymes that can degrade the extracellular matrix and basement membrane collagen for cells to invade (7,8)-and urokinase plasminogen activator (UPA), also play an important role for degrading extracellular matrix (9).…”

Section: Abstract Cantharidin (Ctd) a Component Of Natural Mylabrismentioning

confidence: 99%

“…MMP-2 and -9 have gelatinase activity and can degrade matrix collagen and basement membrane (7,8). It has been reported that estrogen can increase expression of vascular endothelial growth factor (VEGF) and activate the extracellular signal-regulated kinase1/2 (ERK1/2) pathway to induce MMP-2/-9 expression (12).…”

Section: Abstract Cantharidin (Ctd) a Component Of Natural Mylabrismentioning

confidence: 99%

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Cantharidin Impairs Cell Migration and Invasion of Human Lung Cancer NCI-H460 Cells via UPA and MAPK Signaling Pathways

Hsia

Hsiao

et al. 2016

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Abstract. Cantharidin (CTD), a component of natural mylabris (Mylabris phalerata Pallas), has been shown to have biological activities and induce cell death in many human and the results indicated that CTD inhibited the enzymatic activities of MMP-2/-9 of NCI-H460 cells. Western blotting was used to examine the protein expression of NCI-H460 cells after incubation with CTD and the results showed that CTD decreased the expression of MMP-2/-9, focal adhesion kinase (FAK), Ras homolog gene family, member A (Rho A), phospho-protein kinase B (AKT) (Thr308)(p-AKT(308)), phospho-extracellular signal-regulated kinase1/2 (p-ERK1/2), phospho-p38 mitogen-activated protein (MAP) kinase (p-p38), phospho c-Jun N-terminal kinase 1/2 (p-JNK1/2), nuclear factor-ĸB (NF-ĸB) and urokinase plasminogen activator (UPA). Furthermore, confocal laser microscopy was used to confirm that CTD suppressed the expression of NF-ĸB p65, but did not significantly affect protein kinase C (PKC) translocation in NCI-H460 cells. Based on those observations, we suggest that CTD may be used as a novel anticancer metastasis agent for lung cancer in the future.Lung cancer is the most common cancer among women and men in Taiwan and it is the major cause of death in cancerrelated diseases in the developed world. Neoplastic metastasis is a major cause of cancer-mediated death in humans (1, 2). For tumor metastasis, epithelial cancer cells have to migrate from the original primary tumor mass via breaking their cellcell contacts (adherens junctions) to form cancer mass in a new site (3, 4); thus, tumor metastasis involves cell attachment (adhension), migration and invasion in order to form a new tumor in another site of the body. Inhibiting cancer cell metastasis is one of the important steps for cancer therapy and research (5). Numerous evidence have shown that multiple factors involved in tumor metastasis, such as the activation of PI3K/Akt pathway (6), matrix metalloproteinases (MMPs)-enzymes that can degrade the extracellular matrix and 5989

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Section: Abstract Cantharidin (Ctd) a Component Of Natural Mylabrismentioning

confidence: 99%

Section: Abstract Cantharidin (Ctd) a Component Of Natural Mylabrismentioning

confidence: 99%

Cantharidin Impairs Cell Migration and Invasion of Human Lung Cancer NCI-H460 Cells via UPA and MAPK Signaling Pathways

Hsia

Hsiao

et al. 2016

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“…It can rapidly be activated by shear stress and cyclic stretching (Li et al, 1997;Yuan et al, 2012a). Activated ERK1/2 regulates the activity of MMPs, leading to the degradation of ECM and enhanced cell motility (Babykutty et al, 2012;Tan et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

Cyclic mechanical stretching promotes migration but inhibits invasion of rat bone marrow stromal cells

et al. 2015

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Bone marrow stromal cells (BMSCs, also broadly known as bone marrow-derived mesenchymal stem cells) are multipotent stem cells that have a self-renewal capacity and multilineage differentiation potential. Mechanical stretching plays a vital role in regulating the proliferation and differentiation of BMSCs. However, little is known about the effects of cyclic stretching on BMSC migration and invasion. In this study, using a custom-made cell-stretching device, we studied the effects of cyclic mechanical stretching on rat BMSC migration and invasion using a Transwell Boyden Chamber. The protein secretion of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) was detected by gelatin zymography, and the activation of focal adhesion kinase (FAK) and extracellular signal regulated kinase1/2 (ERK1/2) was measured by western blot. We found that cyclic mechanical stretching with 10% amplitude at 1Hz frequency for 8h promotes BMSC migration, but reduces BMSC invasion. FAK and ERK1/2 signals were activated in BMSCs after exposure to cyclic stretching. In the presence of the FAK phosphorylation blocker PF573228 or the ERK1/2 phosphorylation blocker PD98059, the cyclic-stretch-promoted migration of BMSCs was completely suppressed. On the other hand, cyclic mechanical stretching reduced the secretion of MMP-2 and MMP-9 in BMSCs, and PF573228 suppressed the cyclic-stretch-reduced secretion of MMP-2 and MMP-9. The decrease of BMSC invasion induced by mechanical stretching is partially restored by PF573228 but remained unaffected by PD98059. Taken together, these data show that cyclic mechanical stretching promotes BMSC migration via the FAK-ERK1/2 signalling pathway, but reduces BMSC invasion by decreasing secretion of MMP-2 and MMP-9 via FAK, independent of the ERK1/2 signal.

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“…In scratch wound and modified Boyden chamber assays with colorectal carcinoma cell lines, the PKG inhibitor KT5823 effectively halted cell migration induced by NO donor treatment. 27) In contrast to beneficial effects of PKG inhibitors in cancer treatment, one report suggested a pro-apoptotic role for PKG in estrogen receptor-positive (MCF-7) and estrogen receptor-negative (MDA-MB-468) breast cancer cell lines. 28) Therefore, to make use of PKG inhibitors in cancer treatment, a specific classification of the malignancy and precise details of its response to treatment are critical.…”

Section: )mentioning

confidence: 99%

Synthesis and Characterization of 8-Nitroguanosine 3′,5′-Cyclic Monophosphorothioate Rp-Isomer as a Potent Inhibitor of Protein Kinase G1α

Ahmed

Zhang

Ono

et al. 2017

Biological & Pharmaceutical Bulletin

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Guanosine 3′,5′-cyclic monophosphate (cGMP)-dependent protein kinases (PKG) are kinases regulating diverse physiological functions including vascular smooth muscle relaxation, neuronal synaptic plasticity, and platelet activities. Certain PKG inhibitors, such as Rp-diastereomers of derivatives of guanosine 3′,5′-cyclic monophosphorothioate (Rp-cGMPS), have been designed and used to study PKG-regulated cell signaling. 8-Nitroguanosine 3′,5′-cyclic monophosphate (8-nitro-cGMP) is an endogenous cGMP derivative formed as a result of excess production of reactive oxygen species and nitric oxide. 8-Nitro-cGMP causes persistent activation of PKG1α through covalent attachment of cGMP moieties to cysteine residues of the enzyme (i.e., the process called protein S-guanylation). In this study, we synthesized a nitrated analogue of Rp-cGMPS, 8-nitroguanosine 3′,5′-cyclic monophosphorothioate Rp-isomer (Rp-8-nitro-cGMPS), and investigated its effects on PKG1α activity. We synthesized Rp-8-nitro-cGMPS by reacting Rp-8-bromoguanosine 3′,5′-cyclic monophosphorothioate (Rp-8-bromo-cGMPS) with sodium nitrite. Rp-8-Nitro-cGMPS reacted with the thiol compounds cysteine and glutathione to form Rp-8-thioalkoxy-cGMPS adducts to a similar extent as did 8-nitro-cGMP. As an important finding, a protein S-guanylation-like modification was clearly observed, by using Western blotting, in the reaction between recombinant PKG1α and Rp-8-nitro-cGMPS. Rp-8-Nitro-cGMPS inhibited PKG1α activity with an inhibitory constant of 22 µM in a competitive manner. An organ bath assay with mouse aorta demonstrated that Rp-8-nitro-cGMPS inhibited vascular relaxation induced by acetylcholine or 8-bromo-cGMP more than Rp-8-bromo-cGMPS did. These findings suggest that Rp-8-nitro-cGMPS inhibits PKG through induction of an S-guanylation-like modification by attaching the Rp-cGMPS moiety to the enzyme. Additional study is warranted to explore the potential application of Rp-8-nitro-cGMPS to biochemical and therapeutic research involving PKG1α activation.

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Insidious role of nitric oxide in migration/invasion of colon cancer cells by upregulating MMP-2/9 via activation of cGMP-PKG-ERK signaling pathways

Cited by 79 publications

References 69 publications

Cantharidin Impairs Cell Migration and Invasion of Human Lung Cancer NCI-H460 Cells via UPA and MAPK Signaling Pathways

Cantharidin Impairs Cell Migration and Invasion of Human Lung Cancer NCI-H460 Cells via UPA and MAPK Signaling Pathways

Cyclic mechanical stretching promotes migration but inhibits invasion of rat bone marrow stromal cells

Synthesis and Characterization of 8-Nitroguanosine 3′,5′-Cyclic Monophosphorothioate Rp-Isomer as a Potent Inhibitor of Protein Kinase G1α

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