Cilostazol reduces proliferation through c-Myc down-regulation in MDCK cells

Muñoz, Balam; Huerta, Miriam; López-Bayghen, Esther

doi:10.1016/j.ejphar.2009.06.016

Cited by 7 publications

(7 citation statements)

References 46 publications

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“…We also found that the inhibitory effect of cilostazol on the phosphorylation of Raf and ERK significantly depends on PKA activity. This finding is supported by previous reports 38,39) . To investigate whether suppression of the phosphorylation of ERK is associated with direct MEK inhibition induced by cilostazol or other mechanisms, VSMCs were treated simultaneously with 30 M PD98059, a MEK inhibitor, and 100 M cilostazol.…”

Section: Discussionsupporting

confidence: 83%

Inhibitory Effects of Cilostazol on Proliferation of Vascular Smooth Muscle Cells (VSMCs) Through Suppression of the ERK1/2 Pathway

Yoo

Koh

Cho

et al. 2010

JAT

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A Rum Yoo and Seong-Ho Koh contributed equally to this work Aim: The abnormal proliferation of vascular smooth muscle cells (VSMCs) in arterial walls is an important pathogenic factor of vascular disorders such as atherosclerosis and restenosis after angioplasty. During atherogenesis or in response to vessel injury, VSMC proliferation is induced by a number of peptide growth factors released from platelets and VSMCs. Cilostazol is a phosphodiesterase (PDE) 3 inhibitor that increases intracellular cAMP levels and decreases intracellular Ca 2 levels, inhibiting platelet aggregation and inducing vasodilatation. Cilostazol is also known to have an inhibitory effect on the proliferation of VSMCs, but the anti-proliferative mechanism of cilostazol in VSMCs has not yet been established. In the present study, we investigated whether the anti-proliferative mechanism of cilostazol is associated with the suppression of extracellular signal-regulated kinases (ERK) and phosphatidylinositol 3 kinase (PI3K) signaling pathways. Methods: To confirm the anti-proliferative effects of cilostazol on VSMCs, VSMCs were induced to proliferate by serum-induced mitogenesis and then were treated with cilostazol for 24 h. And, to investigate whether the anti-proliferative mechanism of cilostazol in VSMCs involves the suppression of the ERK and PI3K pathways, expression of the phosphorylated forms of ERK1/2, Raf, Akt, and glycogen synthase kinase (GSK)-3 were evaluated by western blot. Results: Cilostazol inhibited VSMC proliferation in a dose-dependent manner. Phosphorylated ERK1/2 and Raf were significantly reduced in a dose-dependent manner, whereas phosphorylated Akt and GSK-3 were not changed. Conclusion: These results suggest that suppression of the ERK pathway but not the PI3K pathway is an important mechanism in the anti-proliferative effect of cilostazol on VSMCs.

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Section: Discussionsupporting

confidence: 83%

Inhibitory Effects of Cilostazol on Proliferation of Vascular Smooth Muscle Cells (VSMCs) Through Suppression of the ERK1/2 Pathway

Yoo

Koh

Cho

et al. 2010

JAT

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“…It has previously been shown that PDE3 inhibitors suppress mitogenesis (Matousovic et al, 1995;Cheng et al, 2004) and proliferation (Chini et al, 1997) of mesangial cells. While cilostazol is one of the most widely used PDE3 inhibitors, it also reduced proliferation of renal tubular epithelial cells (Matousovic et al, 1997;Muñoz and López-Bayghen, 2008). These data provide strong support for the idea that cilostazol may prevent the major pathological changes in kidneys of diabetes, protecting diabetic rats from nephropathy, similar to the proposal by Cheng and Grande (2007), who suggested that PDE inhibitors may be effective agents in treating chronic renal diseases.…”

Section: Discussionsupporting

confidence: 81%

Intervention with cilostazol attenuates renal inflammation in streptozotocin-induced diabetic rats

et al. 2008

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“…In addition, it has been reported to have anti-inflammatory and antiapoptotic effects (12,13), and has reduced restenosis in studies with coronary stents (14 -17). Adjunctive cilostazol treatment on top of the standard DAT (triple antiplatelet therapy [TAT]), in patients with type 2 diabetes mellitus, enhances inhibition of platelet P2Y12 signaling, and cilostazol intensifies platelet inhibition in patients who showed high PPR despite conventional DAT (18,19).…”

Section: See Page 290mentioning

confidence: 98%

Multicenter Randomized Trial Evaluating the Efficacy of Cilostazol on Ischemic Vascular Complications After Drug-Eluting Stent Implantation for Coronary Heart Disease

Suh

Lee

Park

et al. 2011

Journal of the American College of Cardiology

167

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Cilostazol reduces proliferation through c-Myc down-regulation in MDCK cells

Cited by 7 publications

References 46 publications

Inhibitory Effects of Cilostazol on Proliferation of Vascular Smooth Muscle Cells (VSMCs) Through Suppression of the ERK1/2 Pathway

Inhibitory Effects of Cilostazol on Proliferation of Vascular Smooth Muscle Cells (VSMCs) Through Suppression of the ERK1/2 Pathway

Intervention with cilostazol attenuates renal inflammation in streptozotocin-induced diabetic rats

Multicenter Randomized Trial Evaluating the Efficacy of Cilostazol on Ischemic Vascular Complications After Drug-Eluting Stent Implantation for Coronary Heart Disease

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