Ursolic acid inhibits neointima formation in the rat carotid artery injury model

Pozo, Mayte; Castilla, Virginia; Gutiérrez, Cristina; Nicolás, R; Egido, Jesús; González-Cabrero, J

doi:10.1016/j.atherosclerosis.2005.04.014

Cited by 25 publications

(16 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We found that ursolic acid potentiates the apoptotic effect of bortezomib and thalidomide in multiple myeloma cells. Ursolic acid has been shown to be well tolerated in animal studies, with little toxicity (12,69,70). We contend that the apparent pharmacologic safety of ursolic acid and its ability to downregulate the expression of several genes involved in cell survival and chemoresistance provide a sufficient rationale for testing ursolic acid further in patients with multiple myeloma.…”

Section: Discussionmentioning

confidence: 99%

Ursolic Acid Inhibits STAT3 Activation Pathway Leading to Suppression of Proliferation and Chemosensitization of Human Multiple Myeloma Cells

Pathak

Bhutani

Nair

et al. 2007

Molecular Cancer Research

216

137

View full text Add to dashboard Cite

The activation of signal transducers and activators of transcription 3 (STAT3) has been linked with the proliferation of a variety of human cancer cells, including multiple myeloma. Agents that can suppress STAT3 activation have potential for prevention and treatment of cancer. In the present report, we tested an agent, ursolic acid, found in basil, apples, prunes, and cranberries, for its ability to suppress STAT3 activation. We found that ursolic acid, a pentacyclic triterpenoid, inhibited both constitutive and interleukin-6 -inducible STAT3 activation in a dose-and time-dependent manner in multiple myeloma cells. The suppression was mediated through the inhibition of activation of upstream kinases c-Src, Janus-activated kinase 1, Janus-activated kinase 2, and extracellular signalregulated kinase 1/2. Vanadate treatment reversed the ursolic acid -induced down-regulation of STAT3, suggesting the involvement of a tyrosine phosphatase. Indeed, we found that ursolic acid induced the expression of tyrosine phosphatase SHP-1 protein and mRNA. Moreover, knockdown of SHP-1 by small interfering RNA suppressed the induction of SHP-1 and reversed the inhibition of STAT3 activation, thereby indicating the critical role of SHP-1 in the action of this triterpene. Ursolic acid down-regulated the expression of STAT3-regulated gene products such as cyclin D1, Bcl-2, Bcl-xL, survivin, Mcl-1, and vascular endothelial growth factor. Finally, ursolic acid inhibited proliferation and induced apoptosis and the accumulation of cells in G 1 -G 0 phase of cell cycle. This triterpenoid also significantly potentiated the apoptotic effects of thalidomide and bortezomib in multiple myeloma cells. Overall, these results suggest that ursolic acid is a novel blocker of STAT3 activation that may have a potential in prevention and treatment of multiple myeloma and other cancers. (Mol Cancer Res 2007;5(9):943 -55)

show abstract

Section: Discussionmentioning

confidence: 99%

Ursolic Acid Inhibits STAT3 Activation Pathway Leading to Suppression of Proliferation and Chemosensitization of Human Multiple Myeloma Cells

Pathak

Bhutani

Nair

et al. 2007

Molecular Cancer Research

216

137

View full text Add to dashboard Cite

show abstract

“…The vessels were cut into small segments. VSMC were isolated by collagenase type II (Sigma) enzymatic digestion and the explant method [28]. Cell cultures were maintained at 37°C in 5% CO 2 in Dulbecco’s modified minimal essential media (DMEM; Gibco), supplemented with 10% fetal calf serum (FCS), glutamine, penicillin, streptomycin and fungizone.…”

Section: Methodsmentioning

confidence: 99%

Gliotoxin Inhibits Neointimal Hyperplasia after Vascular Injury in Rats

et al. 2008

Self Cite

View full text Add to dashboard Cite

Neointima formation participates in the pathophysiology of atherosclerosis and restenosis. Proliferation and migration of vascular smooth muscle cells (VSMC) are initial responses to vascular injury. The aim of the present study was to assess the effect of gliotoxin, an inhibitor of nuclear factor (NF)-κB, on migration and proliferation of cultured rat VSMC and neointimal formation in injured rat vessels. In cultured VSMC, gliotoxin inhibited the nuclear translocation of the p65 subunit of NF-κB in response to inflammatory stimuli. In addition, gliotoxin inhibited VSMC migration and proliferation in response to platelet-derived growth factor-BB. This was associated with a rapid rearrangement of the F-actin and vimentin cytoskeleton. Furthermore, gliotoxin inhibited endothelial cell nuclear translocation of p65, cell surface expression of adhesion molecules such as VCAM-1, ICAM-1 and E-selectin, and monocytic cell adhesion to a cytokine-activated endothelial monolayer. In the rat carotid artery balloon catheter injury model, the systemic administration of gliotoxin for 10 days decreased neointimal hyperplasia and luminal stenosis by up to 90% and decreased the expression of proliferating cell nuclear antigen in the vessel wall by up to 70%, depending on the dose. These observations suggest that gliotoxin favorably regulates the response to vascular injury through actions on VSMC. However, further studies evaluating the therapeutic benefit of gliotoxin in restenosis after balloon angioplasty are required.

show abstract

“…TNF-induced Eselectin expression is shown to be suppressed by ursolic acid via the inhibition of NF-B [50]. In the rat carotid artery injury model, ursolic acid has been demonstrated to inhibit neointima formation [51]. In contrast, a recent study has shown that oral treatment of apolipoprotein E-knockout mice with ursolic acid for 24 weeks accelerates atherosclerotic plaque formation in a dose-dependent manner [52].…”

Section: Ursolic Acidmentioning

confidence: 99%

Effects of Vasoactive Chinese Herbs on the Endothelial NO System

Li¹

2012

Recent Advances in Theories and Practice of Chinese Medicine

View full text Add to dashboard Cite

Ursolic acid inhibits neointima formation in the rat carotid artery injury model

Cited by 25 publications

References 31 publications

Ursolic Acid Inhibits STAT3 Activation Pathway Leading to Suppression of Proliferation and Chemosensitization of Human Multiple Myeloma Cells

Ursolic Acid Inhibits STAT3 Activation Pathway Leading to Suppression of Proliferation and Chemosensitization of Human Multiple Myeloma Cells

Gliotoxin Inhibits Neointimal Hyperplasia after Vascular Injury in Rats

Effects of Vasoactive Chinese Herbs on the Endothelial NO System

Contact Info

Product

Resources

About