Esculetin inhibits Ras-mediated cell proliferation and attenuates vascular restenosis following angioplasty in rats

Pan, Shiow Lin; Huang, Ying; Guh, Jih‐Hwa; Chang, Ya Ling; Peng, Chieh Yu; Teng, Che-Ming

doi:10.1016/s0006-2952(03)00161-8

Cited by 62 publications

(41 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previous studies have shown the inhibitory effect of esculetin on cell proliferation in many cell lines (31)(32)(33)(34)37). The present study also shows that esculetin inhibits the growth of colon cancer HCT116 cells in a time-and dosedependent manner, as is evident by cell viability and DNA synthesis.…”

Section: Discussionsupporting

confidence: 85%

“…Other studies have also demonstrated the involvement of ERK activation in the esculetininduced inhibition of cell growth in human leukemia cells and VSMCs (32,38,39). Another study has indicated that esculetin induced apoptosis, through the activation of JNK in human leukemia cells (39).…”

Section: Discussionmentioning

confidence: 93%

“…Esculetin, a naturally-occurring coumarin compound, has been shown to have many pharmacological effects associated with cell proliferation (28)(29)(30)(31)(32)(33). It is known to inhibit cancer cell proliferation in both in vitro and in vivo models (34,37).…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies have reported the suppression of xanthine oxidase activity, antioxidant activity, platelet aggregation, the inhibition of human leukemia cell growth and anti-atherogenic activity (28)(29)(30)(31)(32)(33). Although the inhibition of cell growth by esculetin has been observed in cancer cells (34), the mechanism by which esculetin is involved in the cross-link between the Ras/ERK1/2 signaling pathway and cell cycle regulation is not well understood.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Esculetin inhibits cell proliferation through the Ras/ERK1/2 pathway in human colon cancer cells

Park

Park²,

Lim³

et al. 2010

Oncol Rep

View full text Add to dashboard Cite

Abstract. Esculetin, a phenolic compound, has been shown to inhibit the growth of colon tumors in animal studies. However, the roles of signaling pathways and cell cycle regulation in the esculetin-induced inhibition of cancer cell growth, remain to be elucidated. The present study suggests a novel mechanism for the Ras/ERK1/2 pathway in esculetintreated human colon cancer HCT116 cells. The treatment of cells with esculetin resulted in significant growth inhibition and G1 phase cell cycle arrest, which led to the downregulation of cyclin and cyclin-dependent kinase (CDK) expressions. This G1 phase cell cycle arrest was associated with the up-regulation of p27KIP expression. In addition, ERK1/2 was activated by esculetin. The pre-treatment of cells with the MEK1/2-specific inhibitor, PD98059, blocked the p27KIP expression induced by esculetin. Blockage of the ERK1/2 function consistently prevented the inhibition of cell proliferation and decreased G1 phase cell cycle protein levels. Furthermore, Ras activation was increased by the esculetin treatment. Transient transfection of the dominant negative Ras (RasN17) mutant gene abolished both the ERK1/2 activity and p27KIP expression induced by esculetin. Finally, the overexpression of RasN17 suppressed the esculetininduced reduction in cell proliferation and cell cycle proteins. In conclusion, these results indicate that the Ras/ERK1/2 pathway is mediated by the p27KIP1 induction, leading to a reduction in cyclin/CDK complexes in the esculetin-induced inhibition of colon cancer cell growth. Overall, these findings indicate that the molecular action of esculetin has therapeutic potential for the treatment of colon malignancies.

show abstract

Section: Discussionsupporting

confidence: 85%

Section: Discussionmentioning

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Esculetin inhibits cell proliferation through the Ras/ERK1/2 pathway in human colon cancer cells

Park

Park²,

Lim³

et al. 2010

Oncol Rep

View full text Add to dashboard Cite

show abstract

“…We used the established rat carotid artery (CA) model of balloon angioplasty to examine the in vivo arterial response to injury (Pan et al, 2003). Briefly, male Wistar rats weighing an average of 300 g were anesthetized with pentobarbital (60 mg/kg), and the left CA was exposed.…”

Section: Methodsmentioning

confidence: 99%

YC-1 [3-(5′-Hydroxymethyl-2′-furyl)-1-benzyl Indazole] Inhibits Neointima Formation in Balloon-Injured Rat Carotid through Suppression of Expressions and Activities of Matrix Metalloproteinases 2 and 9

Liu¹,

Pan²,

Peng³

et al. 2005

J Pharmacol Exp Ther

Self Cite

View full text Add to dashboard Cite

Matrix metalloproteinases (MMPs), particularly MMP-2 and MMP-9, and postrevascularization production of vascular smooth muscle cells may play key roles in development of arterial restenosis. We investigated the inhibitory effect of 3-(5Ј-hydroxymethyl-2Ј-furyl)-1-benzyl indazole (YC-1), a benzyl indazole compound, on MMP-2 and MMP-9 activity in a ballooninjury rat carotid artery model. Injury was induced by inserting a balloon catheter through the common carotid artery; after 14 days, histopathological analysis using immunostaining and Western blotting revealed significant restenosis with neointimal formation that was associated with enhanced protein expression of MMP-2 and MMP-9. However, these effects were dosedependently reduced by orally administered YC-1 (1-10 mg/ kg). In addition, gelatin zymography demonstrated that increased MMP-2 and MMP-9 activity was diminished by YC-1 treatment. On the other hand, YC-1 inhibited hydrolysis of the fluorogenic quenching substrate Mca-Pro-Leu-Gly-Leu-DpaAla-Arg-NH 2 by recombinant MMP-2 and MMP-9 with IC 50 values ϭ 2.07 and 8.20 M, respectively. Reverse transcription-polymerase chain reaction analysis of MMP-2 and MMP-9 mRNA revealed that YC-1 significantly inhibited mRNA levels of MMPs. Finally, for the YC-1 treatment group, we did not observe elevation of cGMP levels using enzyme-linked immunosorbent assay, suggesting that YC-1 inhibition of neointimal formation is not through a cGMP-elevating pathway. These data show YC-1 suppression of neointimal formation is dependent on its influence on MMP-2 and MMP-9 protein, mRNA expression, and activity, but not through a cGMP-elevating effect. YC-1 shows therapeutic potential for treatment of restenosis after angioplasty.During the past 20 years, one focus of cardiovascular pharmaceutical research has been the development of drugs that inhibit intimal hyperplasia. Despite many attempts, no clinical trial has proven that there is an effective pharmacological solution to the problem (Bult, 2000;Garas et al., 2001). Intimal hyperplasia is a late response of the arterial wall to mechanical injury, and it is a major cause of restenosis after percutaneous transluminal coronary angioplasty (Lange et al., 1991). After vascular injury, inflammatory cells are recruited to the lesion, where they release several mitogens that activate vascular smooth muscle cells (VSMCs). Consequently, VSMCs are capable of proliferating and migrating from media to intima, releasing matrix and resulting in neointima formation.Matrix metalloproteinases (MMPs) are a family of structurally related zinc-endopeptidases that degrade components of extracellular matrix associated with vascular remodeling during vascular injury-induced neointima formation (Pauly et al., 1994;Lijnen et al., 1999). MMP-2 and MMP-9, also called gelatinases A and B, respectively, are the major MMPs

show abstract

Esculetin: A review of its pharmacology and pharmacokinetics

Zhang

Xie

2021

Phytotherapy Research

View full text Add to dashboard Cite

Esculetin is a natural dihydroxy coumarin; it is mainly extracted from twig skin and the trunk bark of the Chinese herbal medicine Fraxinus rhynchophylla Hance. Emerging evidence suggests that esculetin has a wide range of pharmacological activities.Based on its fundamental properties, including antioxidant, antiinflammatory, antiapoptotic, anticancer, antidiabetic, neuroprotective, and cardiovascular protective activities, as well as antibacterial activity, among others, esculetin is expected to be a therapeutic drug for specific disease indications, such as cancer, diabetes, atherosclerosis, Alzheimer's disease (AD), Parkinson's disease (PD), nonalcoholic fatty liver disease (NAFLD), and other diseases. The oral bioavailability of esculetin was shown by studies to be low. The extensive glucuronidation was described to be the main metabolic pathway of esculetin and C-7 phenolic hydroxyl to be its major metabolic site.With the development of scientific research technology, the pharmacological effects of esculetin are identified and its potential for the treatment of diseases is demonstrated. The underlining mechanisms of action and biological activities as well as the pharmacokinetic data of the analyzed compound reported so far are highlighted in this review with the aim of becoming a proven, and applicable insight and reference for further studies on the utilization of esculetin.

show abstract

Esculetin inhibits Ras-mediated cell proliferation and attenuates vascular restenosis following angioplasty in rats

Cited by 62 publications

References 26 publications

Esculetin inhibits cell proliferation through the Ras/ERK1/2 pathway in human colon cancer cells

Esculetin inhibits cell proliferation through the Ras/ERK1/2 pathway in human colon cancer cells

YC-1 [3-(5′-Hydroxymethyl-2′-furyl)-1-benzyl Indazole] Inhibits Neointima Formation in Balloon-Injured Rat Carotid through Suppression of Expressions and Activities of Matrix Metalloproteinases 2 and 9

Esculetin: A review of its pharmacology and pharmacokinetics

Contact Info

Product

Resources

About