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Murrayafoline A Induces a G0/G1-Phase Arrest in Platelet-Derived Growth Factor-Stimulated Vascular Smooth Muscle Cells.

Han JH, Kim Y, Jung SH, Lee JJ, Park HS, Song GY, Cuong NM, Kim YH, Myung CS - Korean J. Physiol. Pharmacol. (2015)

Bottom Line: Abnormally high activity of platelet-derived growth factor (PDGF) is believed to play a central role in the etiology of these pathophysiological situations.Here, we investigated the anti-proliferative effects and possible mechanism(s) of murrayafoline A, a carbazole alkaloid isolated from Glycosmis stenocarpa Guillamin (Rutaceae), on PDGF-BB-stimulated VSMCs.These results indicate that murrayafoline A may be useful in preventing the progression of vascular complications such as restenosis after percutaneous transluminal coronary angioplasty and atherosclerosis.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology, Chungnam National University College of Pharmacy, Daejeon 305-764, Korea.

ABSTRACT
The increased potential for vascular smooth muscle cell (VSMC) growth is a key abnormality in the development of atherosclerosis and post-angioplasty restenosis. Abnormally high activity of platelet-derived growth factor (PDGF) is believed to play a central role in the etiology of these pathophysiological situations. Here, we investigated the anti-proliferative effects and possible mechanism(s) of murrayafoline A, a carbazole alkaloid isolated from Glycosmis stenocarpa Guillamin (Rutaceae), on PDGF-BB-stimulated VSMCs. Murrayafoline A inhibited the PDGF-BB-stimulated proliferation of VSMCs in a concentration-dependent manner, as measured using a non-radioactive colorimetric WST-1 assay and direct cell counting. Furthermore, murrayafoline A suppressed the PDGF-BB-stimulated progression through G0/G1 to S phase of the cell cycle, as measured by [(3)H]-thymidine incorporation assay and cell cycle progression analysis. This anti-proliferative action of murrayafoline A, arresting cell cycle progression at G0/G1 phase in PDGF-BB-stimulated VSMCs, was mediated via down-regulation of the expression of cyclin D1, cyclin E, cyclin-dependent kinase (CDK)2, CDK4, and proliferating cell nuclear antigen (PCNA), and the phosphorylation of retinoblastoma protein (pRb). These results indicate that murrayafoline A may be useful in preventing the progression of vascular complications such as restenosis after percutaneous transluminal coronary angioplasty and atherosclerosis.

No MeSH data available.


Related in: MedlinePlus

Effects of murrayafoline A on the PDGF-BB-stimulated activation of PDGF-Rβ, PLCγ1, Akt, ERK1/2, and STAT3. Quiescent VSMCs cultured in serum-free medium were stimulated with 50 ng/ml PDGF-BB, and the effects of various concentrations of murrayafoline A (1-5 µM) in changing the PDGF-BB-induced phosphorylation of PDGF-Rβ, PLCγ1, Akt, ERK1/2, and STAT3 were measured as described in the Experimental Section.
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Figure 2: Effects of murrayafoline A on the PDGF-BB-stimulated activation of PDGF-Rβ, PLCγ1, Akt, ERK1/2, and STAT3. Quiescent VSMCs cultured in serum-free medium were stimulated with 50 ng/ml PDGF-BB, and the effects of various concentrations of murrayafoline A (1-5 µM) in changing the PDGF-BB-induced phosphorylation of PDGF-Rβ, PLCγ1, Akt, ERK1/2, and STAT3 were measured as described in the Experimental Section.

Mentions: Since PDGF-BB has been known to activate the PLCγ1, protein kinase B (Akt/PKB), ERK1/2, and STAT3 pathways [142021], we examined the inhibitory effects of murrayafoline A on the levels of phosphorylated PDGF receptor β (PDGF-Rβ) and mitogens downstream of PDGF-Rβ signaling pathways. Interestingly, pretreatment of the cells with murrayafoline A did not show any detectable effect on PDGF-Rβ, PLCγ1, Akt, ERK1/2, and STAT3 in PDGF-BB-stimulated VSMCs (Fig. 2). Therefore, these results suggest that the PDGF-Rβ, PLCγ1, Akt, ERK1/2, and STAT3 pathways are not involved in the murrayafoline A-induced inhibition of PDGF-BB-stimulated VSMC proliferation.


Murrayafoline A Induces a G0/G1-Phase Arrest in Platelet-Derived Growth Factor-Stimulated Vascular Smooth Muscle Cells.

Han JH, Kim Y, Jung SH, Lee JJ, Park HS, Song GY, Cuong NM, Kim YH, Myung CS - Korean J. Physiol. Pharmacol. (2015)

Effects of murrayafoline A on the PDGF-BB-stimulated activation of PDGF-Rβ, PLCγ1, Akt, ERK1/2, and STAT3. Quiescent VSMCs cultured in serum-free medium were stimulated with 50 ng/ml PDGF-BB, and the effects of various concentrations of murrayafoline A (1-5 µM) in changing the PDGF-BB-induced phosphorylation of PDGF-Rβ, PLCγ1, Akt, ERK1/2, and STAT3 were measured as described in the Experimental Section.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4553401&req=5

Figure 2: Effects of murrayafoline A on the PDGF-BB-stimulated activation of PDGF-Rβ, PLCγ1, Akt, ERK1/2, and STAT3. Quiescent VSMCs cultured in serum-free medium were stimulated with 50 ng/ml PDGF-BB, and the effects of various concentrations of murrayafoline A (1-5 µM) in changing the PDGF-BB-induced phosphorylation of PDGF-Rβ, PLCγ1, Akt, ERK1/2, and STAT3 were measured as described in the Experimental Section.
Mentions: Since PDGF-BB has been known to activate the PLCγ1, protein kinase B (Akt/PKB), ERK1/2, and STAT3 pathways [142021], we examined the inhibitory effects of murrayafoline A on the levels of phosphorylated PDGF receptor β (PDGF-Rβ) and mitogens downstream of PDGF-Rβ signaling pathways. Interestingly, pretreatment of the cells with murrayafoline A did not show any detectable effect on PDGF-Rβ, PLCγ1, Akt, ERK1/2, and STAT3 in PDGF-BB-stimulated VSMCs (Fig. 2). Therefore, these results suggest that the PDGF-Rβ, PLCγ1, Akt, ERK1/2, and STAT3 pathways are not involved in the murrayafoline A-induced inhibition of PDGF-BB-stimulated VSMC proliferation.

Bottom Line: Abnormally high activity of platelet-derived growth factor (PDGF) is believed to play a central role in the etiology of these pathophysiological situations.Here, we investigated the anti-proliferative effects and possible mechanism(s) of murrayafoline A, a carbazole alkaloid isolated from Glycosmis stenocarpa Guillamin (Rutaceae), on PDGF-BB-stimulated VSMCs.These results indicate that murrayafoline A may be useful in preventing the progression of vascular complications such as restenosis after percutaneous transluminal coronary angioplasty and atherosclerosis.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology, Chungnam National University College of Pharmacy, Daejeon 305-764, Korea.

ABSTRACT
The increased potential for vascular smooth muscle cell (VSMC) growth is a key abnormality in the development of atherosclerosis and post-angioplasty restenosis. Abnormally high activity of platelet-derived growth factor (PDGF) is believed to play a central role in the etiology of these pathophysiological situations. Here, we investigated the anti-proliferative effects and possible mechanism(s) of murrayafoline A, a carbazole alkaloid isolated from Glycosmis stenocarpa Guillamin (Rutaceae), on PDGF-BB-stimulated VSMCs. Murrayafoline A inhibited the PDGF-BB-stimulated proliferation of VSMCs in a concentration-dependent manner, as measured using a non-radioactive colorimetric WST-1 assay and direct cell counting. Furthermore, murrayafoline A suppressed the PDGF-BB-stimulated progression through G0/G1 to S phase of the cell cycle, as measured by [(3)H]-thymidine incorporation assay and cell cycle progression analysis. This anti-proliferative action of murrayafoline A, arresting cell cycle progression at G0/G1 phase in PDGF-BB-stimulated VSMCs, was mediated via down-regulation of the expression of cyclin D1, cyclin E, cyclin-dependent kinase (CDK)2, CDK4, and proliferating cell nuclear antigen (PCNA), and the phosphorylation of retinoblastoma protein (pRb). These results indicate that murrayafoline A may be useful in preventing the progression of vascular complications such as restenosis after percutaneous transluminal coronary angioplasty and atherosclerosis.

No MeSH data available.


Related in: MedlinePlus