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. 2013 Sep;57(9):1611-8.
doi: 10.1002/mnfr.201200852. Epub 2013 Apr 2.

Bisdemethoxycurcumin inhibits PDGF-induced vascular smooth muscle cell motility and proliferation

Affiliations

Bisdemethoxycurcumin inhibits PDGF-induced vascular smooth muscle cell motility and proliferation

Yinan Hua et al. Mol Nutr Food Res. 2013 Sep.

Abstract

Scope: A key event in the development of plaque in the arteries is the migration and proliferation of smooth muscle cells (SMCs) from the media to the intima of the blood vessel. This study was conducted to evaluate the effects of bisdemethoxycurcumin (BC), a naturally occurring structural analog of curcumin (CC), on platelet-derived growth factor (PDGF)-stimulated migration and proliferation of SMCs.

Methods and results: CC and BC were synthesized by condensing acetyl acetone with vanillin and 4-hydroxybenzaldehyde, respectively. SMCs isolated from adult rat aorta were stimulated with PDGF in the presence or absence of CC or BC following which, cell migration and proliferation were assessed by monolayer wound healing assay and [(3) H]-thymidine incorporation respectively. PDGF-stimulated phosphorylation of PDGF receptor-β and its downstream effectors Akt and ERK were assessed by Western blotting. Intracellular reactive oxygen species was assessed using the fluorescent dye 5-(6)-chloromethyl-2',7'-dichlorodihydrofluorescein diacetate. BC elicited a concentration-dependent inhibition of PDGF-stimulated phosphorylation of PDGF receptor-β, Akt and Erk as well as the PDGF-stimulated SMC migration and proliferation. BC was more potent than CC in inhibiting migration and proliferation and suppressing PDGF-signaling in SMCs. Both compounds were equipotent in inhibiting PDGF-stimulated generation of intracellular reactive oxygen species.

Conclusion: BC may be of potential use in the prevention or treatment of vascular disease.

Keywords: Curcumin; Migration; Platelet-derived growth factor; Proliferation; Vascular smooth muscle cell.

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Figures

Figure 1
Figure 1
Chemical structures of curcumin and bisdemethoxycurcumin.
Figure 2
Figure 2
A. Bisdemethoxycurcumin (BC) attenuates PDGF (10 ng/mL)-stimulated VSMC motility VSMC motility the monolayer wound-healing assay. Data are mean ± SEM (n=6) and represents the average wound width covered in each treatment group *p<0.001 compared to untreated, #p<0.01 compared to PDGF. B. Inhibition of PDGF (10 ng/mL)-stimulated cell migration by BC and curcumin (CC). Data are mean ± SEM and represents the average wound width covered in each treatment group *p<0.001 compared to untreated, #p<0.01 compared to PDGF, &p<0.05 compared to PDGF +CC.
Figure 2
Figure 2
A. Bisdemethoxycurcumin (BC) attenuates PDGF (10 ng/mL)-stimulated VSMC motility VSMC motility the monolayer wound-healing assay. Data are mean ± SEM (n=6) and represents the average wound width covered in each treatment group *p<0.001 compared to untreated, #p<0.01 compared to PDGF. B. Inhibition of PDGF (10 ng/mL)-stimulated cell migration by BC and curcumin (CC). Data are mean ± SEM and represents the average wound width covered in each treatment group *p<0.001 compared to untreated, #p<0.01 compared to PDGF, &p<0.05 compared to PDGF +CC.
Figure 3
Figure 3
A. Bisdemethoxycurcumin (BC) inhibits PDGF-stimulated VSMC proliferation. Cells were treated with PDGF (10ng/mL) for 24 hours in the presence or absence of BC, and incorporation of [3H]-thymidine was monitored and normalized to protein. Results are the mean ± SE from 3 independent experiments. *p<0.001 compared to untreated, #p<0.01 compared to PDGF. B. Inhibition of PDGF (10 ng/mL)-stimulated cell proliferation by BC and curcumin (CC). Data are mean ± SEM *p<0.001 compared to untreated, #p<0.01 compared to PDGF, &p<0.05 compared to PDGF + corresponding concentrations of CC.
Figure 4
Figure 4
Effect of curcumin and bisdemethoxycurcumin viability of VSMC. Curcumin and bisdemethoxycurcumin were tested at concentrations of 10 and 25 μM for its effect on cell viability using the MTT assay. Mean ± SEM, n = 4.
Figure 5
Figure 5
Effect of bisdemethoxycurcumin (BC) and curcumin (CC) on PDGF (10 ng/mL)– stimulated tyrosine phosphorylation of PDGFR β, serine (473) phosphorylation Akt and phospho Erk in VSMCs. Cells were treated with or without (control) CC of BC (10 μM) for 30 minutes and stimulated with PDGF (10 ng/mL) for 10 minutes. Cells were lysed, and lysates were immuno-blotted with antibodies directed against phospho-PDGF receptor β, phospho-Akt and phospho-Erk. A. Representative Western blot image showing phospho-PDGF receptor β, phospho-Akt and phospho-Erk together with the total proteins. B-D. Relative densities of phosphorylated PDGF receptor β, phosphorylated Akt and phospho-Erk normalized to total proteins. Data are mean + SEM (n=3) of the *p<0.001 compared to untreated, #p<0.01 compared to PDGF, &p<0.05 compared to PDGF compared to PDGF + CC.
Figure 6
Figure 6
Scavenging of PDGF (10 ng/mL)-generated intracellular ROS by bisdemethoxycurcumin (BC) and curcumin (CC) assessed as DCF fluorescence. Data are mean ± SEM (n=3) of the relative fluorescence intensities. *p<0.001 compared to untreated, #p<0.01 compared to PDGF.
Figure 7
Figure 7
Cellular-uptake of curcumin and bisdemethoxycurcumin. VSMCs were treated with various concentrations of curcumin and the cellular uptake of the compounds was assessed by spectrophotometry at 400 nm. The concentrations were calculated for a standard curve generated by using various concentrations of these compounds in ethanol.

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