Resveratrol Inhibits Monocytic Cell Chemotaxis to MCP-1 and Prevents Spontaneous Endothelial Cell Migration Through Rho Kinase-Dependent Mechanism

Cicha, Iwona; Regler, Melanie; Urschel, Katharina; Goppelt‐Struebe, Margarete; Daniel, Werner G.; Garlichs, Christoph D.

doi:10.5551/jat.8136

Cited by 23 publications

(16 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the current study, based on the observation that resveratrol activated RhoA in glioblastoma cells, and that blockade of the RhoA/ROCK pathway attenuated the resveratrol-induced inhibition of cell migration and invasion, we hypothesize that the inhibitory effect of resveratrol on migration and invasion in glioblastoma cells may be mediated through the RhoA/ROCK pathway. A similar finding was reported in human umbilical vein endothelial cells, in which resveratrol inhibited cell migration through a RhoA/ROCK-dependent mechanism (38). With regard to the effect of the RhoA/ROCK pathway on MMP-2, however, there have been controversial reports: Inhibition of RhoA/ROCK was observed to increase MMP-2 expression and activity in microvascular endothelial cells, whereas MMP-2 activity was decreased in osteosarcoma cells (39,40).…”

Section: A B C D Discussionsupporting

confidence: 47%

Resveratrol suppresses human glioblastoma cell migration and invasion via activation of RhoA/ROCK signaling pathway

et al. 2015

View full text Add to dashboard Cite

Abstract. Numerous studies have demonstrated that resveratrol has a potential use in cancer prevention and treatment. However, the effects of resveratrol on cancer cell motility and invasiveness remain unclear. The current study aimed to examine the effects of resveratrol on cell migration and invasion in human glioblastoma cells, and to explore the underlying molecular mechanisms. In wound-healing and Matrigel transwell assays, resveratrol was found to significantly inhibit the migration and invasion of U87MG, T98G and U251 glioblastoma cells in vitro. Results from western blot analysis and gelatin zymography revealed that resveratrol also suppressed the expression and activity of matrix metalloproteinase 2 (MMP-2; P<0.05), an important mediator of cell migration and invasion. Furthermore, using a pull-down assay, increased activation of RhoA was observed in glioblastoma cells treated with resveratrol vs. controls (P<0.05). Notably, inhibition of the RhoA/Rho-associated kinase (ROCK) pathway by C3 transferase or Y-27362 was found to attenuate the resveratrol-induced reductions in cell migration and invasion (P<0.05), and also partially rescued the decreased expression and activity of MMP-2 induced by resveratrol (P<0.05). Taken together, the results suggest that resveratrol may inhibit glioblastoma cell motility and invasiveness via activating the RhoA/ROCK signaling pathway. IntroductionGlioblastoma is the most common and lethal intracranial malignant tumor with a yearly incidence of 3-4 per 100,000 (1). Despite the use of multimodal treatments, the prognosis of glioblastoma has been little improved, with a typical median survival time of only 12-15 months (2). Due to the diffuse infiltration of glioblastoma cells into the brain tissues, resection of the bulk tumor is typically followed by tumor reinitiation at the resection site or at another location in the brain. The highly aggressive and invasive properties of glioblastoma cells contribute significantly to the poor prognosis of cases involving this type of tumor (3). Therefore, it has been proposed that anti-invasion agents may play a crucial role in the treatment of glioblastoma (4).The invasion of malignant cancer cells is favored by degradation of the extracellular matrix (ECM), upregulation of proteolytic enzyme activity and an increase in tumor cell motility and invasive ability (5,6). Accumulating evidence has suggested that matrix metalloproteinases (MMPs) are capable of promoting tumor invasion and metastasis via degradation of the ECM (7), among which two gelatinases, MMP-2 and MMP-9, have attracted the most attention (8). Rho GTPases are a family of small GTP-binding proteins that serve as molecular switches in a wide variety of cellular signaling pathways, ultimately inducing changes in the organization of the actin cytoskeleton and regulating cell motility (9). It has been reported that RhoA activity is significantly reduced in astrocytic tumors (10-12), and increased RhoA activity in glioblastoma cells has been associated with impaired cell mi...

show abstract

Section: A B C D Discussionsupporting

confidence: 47%

Resveratrol suppresses human glioblastoma cell migration and invasion via activation of RhoA/ROCK signaling pathway

et al. 2015

View full text Add to dashboard Cite

show abstract

“…Our results also demonstrated that low doses of resveratrol attenuated the impairment of BAEC migration caused by inflammatory conditions, suggesting a mechanism for its anti-inflammatory properties. Cicha et al [35] observed that resveratrol dose-dependently inhibited EC migration at 1–20 μ mol/L in a Rho-associated-kinase- (ROCK-) dependent manner. Resveratrol promoted proliferation and migration of cerebral by activation of phosphoinositide 3 kinase (PI3-K)/Akt and mitogen-activated protein kinase (MAPK)/ERK signaling pathways [36].…”

Section: Discussionmentioning

confidence: 99%

Protective Effects of Resveratrol on TNF-α-Induced Endothelial Cytotoxicity in Baboon Femoral Arterial Endothelial Cells

Xiao

Song

Hodara

et al. 2013

Journal of Diabetes Research

View full text Add to dashboard Cite

Endothelial injury induced by inflammatory factors plays a critical role in the pathogenesis of cardiovascular disease. Endothelial cell (EC) apoptosis, proliferation, migration, and cellular adhesion molecule (CAM) expression contribute to the development of atherosclerosis. We investigated the effects of resveratrol (0.1–100 μM) on the proliferation, migration, and CAM expression of primary cultures of baboon arterial endothelial cells (BAECs). In addition, we tested its effects under normal conditions as well as under inflammatory conditions induced by tumour necrosis factor-α (TNF-α) administered either by cotreatment, pretreatment, or posttreatment. Immunocytochemistry, MTT, wound-healing, and flow cytometry assays were performed. The resveratrol treatment significantly enhanced BAEC proliferation and attenuated TNF-α-induced impairment of proliferation at the optimal doses of 1–50 µM. Resveratrol at a high dose (100 μM) and TNF-α impaired BAEC migration, while low doses of resveratrol (1–50 μM) attenuated TNF-α-induced impairment of BAEC migration. Moreover, resveratrol inhibited TNF-α-induced ICAM-1 and VCAM-1 expression. Taken together, our results suggest that the resveratrol protects BAECs after inflammatory stimulation as well as ameliorates inflammatory effects at low concentrations. Consequently, resveratrol should be considered as a candidate drug for the prevention and treatment of inflammatory vascular diseases.

show abstract

“…THP-1 monocytic cell recruitment by TNF-α-stimulated human umbilical vein endothelial cells (HUVECs) under flow conditions, in the presence or absence of SPIONdex, was assessed using bifurcating flow-through cell culture slides (Ibidi ® , Munich, Germany) and a programmed peristaltic pump (Ismatec, Wertheim, Germany), as previously reported. 32 The effect of SPIONdex on THP-1 monocytic cell migration was investigated using 96-well Chemo-Tx plates (NeuroProbe, Gaithersburg, MD, USA) and on HUVEC migration, using silicone cell culture inserts (Ibidi, Munich, Germany) and a live-cell imaging microscope, as described in detail in the Supplementary materials. The use of human material was approved by the local ethics committee (Klinisches Ethikkomitee des Universitätsklinikums Erlangen).…”

Section: Spiondex Effect On Endothelial Cells and Leukocytesmentioning

confidence: 99%

Non-immunogenic dextran-coated superparamagnetic iron oxide nanoparticles: a biocompatible, size-tunable contrast agent for magnetic resonance imaging

Unterweger

Janko

Schwarz

et al. 2017

IJN

Self Cite

View full text Add to dashboard Cite

Iron oxide-based contrast agents have been in clinical use for magnetic resonance imaging (MRI) of lymph nodes, liver, intestines, and the cardiovascular system. Superparamagnetic iron oxide nanoparticles (SPIONs) have high potential as a contrast agent for MRI, but no intravenous iron oxide-containing agents are currently approved for clinical imaging. The aim of our work was to analyze the hemocompatibility and immuno-safety of a new type of dextran-coated SPIONs (SPIONdex) and to characterize these nanoparticles with ultra-high-field MRI. Key parameters related to nanoparticle hemocompatibility and immuno-safety were investigated in vitro and ex vivo. To address concerns associated with hypersensitivity reactions to injectable nanoparticulate agents, we analyzed complement activation-related pseudoallergy (CARPA) upon intravenous administration of SPIONdex in a pig model. Furthermore, the size-tunability of SPIONdex and the effects of size reduction on their biocompatibility were investigated. In vitro, SPIONdex did not induce hemolysis, complement or platelet activation, plasma coagulation, or leukocyte procoagulant activity, and had no relevant effect on endothelial cell viability or endothelial–monocytic cell interactions. Furthermore, SPIONdex did not induce CARPA even upon intravenous administration of 5 mg Fe/kg in pigs. Upon SPIONdex administration in mice, decreased liver signal intensity was observed after 15 minutes and was still detectable 24 h later. In addition, by changing synthesis parameters, a reduction in particle size <30 nm was achieved, without affecting their hemo- and biocompatibility. Our findings suggest that due to their excellent biocompatibility, safety upon intravenous administration and size-tunability, SPIONdex particles may represent a suitable candidate for a new-generation MRI contrast agent.

show abstract

Resveratrol Inhibits Monocytic Cell Chemotaxis to MCP-1 and Prevents Spontaneous Endothelial Cell Migration Through Rho Kinase-Dependent Mechanism

Cited by 23 publications

References 37 publications

Resveratrol suppresses human glioblastoma cell migration and invasion via activation of RhoA/ROCK signaling pathway

Resveratrol suppresses human glioblastoma cell migration and invasion via activation of RhoA/ROCK signaling pathway

Protective Effects of Resveratrol on TNF-α-Induced Endothelial Cytotoxicity in Baboon Femoral Arterial Endothelial Cells

Non-immunogenic dextran-coated superparamagnetic iron oxide nanoparticles: a biocompatible, size-tunable contrast agent for magnetic resonance imaging

Contact Info

Product

Resources

About