Evodiamine inhibits PDGF‑BB‑induced proliferation of rat vascular smooth muscle cells through the suppression of cell cycle progression and oxidative stress

Ge,Xie; Chen,Si‑Yu; Liu,Mei; Liang,Ting‑Ming; Liu,Chang

doi:10.3892/mmr.2016.5798

Evodiamine inhibits PDGF‑BB‑induced proliferation of rat vascular smooth muscle cells through the suppression of cell cycle progression and oxidative stress

Authors:
- Xie Ge
- Si‑Yu Chen
- Mei Liu
- Ting‑Ming Liang
- Chang Liu
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Affiliations: Jiangsu Key Laboratory for Molecular and Medical Biotechnology and College of Life Sciences, Nanjing Normal University, Nanjing, Jiangsu 210023, P.R. China
Published online on: October 5, 2016 https://doi.org/10.3892/mmr.2016.5798
Pages: 4551-4558
Copyright: © Ge et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Vascular smooth muscle cell (VSMC) proliferation is a key event in the development of in‑stent restenosis. Evodiamine is an indole alkaloid extracted from the Chinese medicine, evodia, and has been shown to inhibit tumor cell proliferation and protect the cardiovascular system. However, whether evodiamine affects VSMC proliferation remains to be elucidated. Therefore, the present study examined the effects and the mechanisms of action of evodiamine on the proliferation of rat VSMCs. The cells were treated with evodiamine alone or in combination with platelet‑derived growth factor‑BB (PDGF‑BB) stimulation. It was found that evodiamine inhibited PDGF‑BB‑induced VSMC proliferation in a dose‑dependent manner, without inducing cell death. Evodiamine also retarded cell cycle progression, evidenced by the suppression of the expression of cell cycle‑promoting cyclin proteins and cyclin‑dependent kinases. In addition, evodiamine attenuated the PDGF‑BB‑induced phosphorylation of mitogen‑activated protein kinases p38 and extracellular signal‑regulated kinases 1/2, however, it had no effect on the phosphorylation of Akt. Evodiamine also inhibited the increase of reactive oxygen species generation and upregulated the mRNA expression levels of genes encoding antioxidant enzymes. These findings provide important insights into the mechanisms underlying the vasoprotective actions of evodiamine and suggest that it may be a useful therapeutic agent for the treatment of vascular occlusive disease.

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1	Curcio A, Torella D and Indolfi C: Mechanisms of smooth muscle cell proliferation and endothelial regeneration after vascular injury and stenting: Approach to therapy. Circ J. 75:1287–1296. 2011. View Article : Google Scholar : PubMed/NCBI
2	Boucher P and Gotthardt M: LRP and PDGF signaling: A pathway to atherosclerosis. Trends Cardiovasc Med. 14:55–60. 2004. View Article : Google Scholar : PubMed/NCBI
3	Rensen SS, Doevendans PA and van Eys GJ: Regulation and characteristics of vascular smooth muscle cell phenotypic diversity. Neth Heart J. 15:100–108. 2007. View Article : Google Scholar : PubMed/NCBI
4	Park ES, Lee KP, Jung SH, Lee DY, Won KJ, Yun YP and Kim B: Compound K, an intestinal metabolite of ginsenosides, inhibits PDGF-BB-induced VSMC proliferation and migration through G1 arrest and attenuates neointimal hyperplasia after arterial injury. Atherosclerosis. 228:53–60. 2013. View Article : Google Scholar : PubMed/NCBI
5	Palmieri C, Ravani M, Trianni G, Gianetti J, Vaghetti M, Rizza A, Paradossi U, Beqiri A and Berti S: Drug-eluting stents versus bare-metal stents in acute ST-segment elevation myocardial infarction. A single-center experience with long-term follow up. J Invasive Cardiol. 22:151–158. 2010.PubMed/NCBI
6	Rosner D, McCarthy N and Bennett M: Rapamycin inhibits human in stent restenosis vascular smooth muscle cells independently of pRB phosphorylation and p53. Cardiovasc Res. 66:601–610. 2005. View Article : Google Scholar : PubMed/NCBI
7	Nguyen KT, Shaikh N, Wawro D, Zhang S, Schwade ND, Eberhart RC and Tang L: Molecular responses of vascular smooth muscle cells to paclitaxel-eluting bioresorbable stent materials. J Biomed Mater Res A. 69:513–524. 2004. View Article : Google Scholar : PubMed/NCBI
8	Zhao FH, Chen YD, Jin ZN and Lu SZ: Are impaired endothelial progenitor cells involved in the processes of late in-stent thrombosis and re-endothelialization of drug-eluting stents? Med Hypotheses. 70:512–514. 2008. View Article : Google Scholar : PubMed/NCBI
9	Fei XF, Wang BX, Li TJ, Tashiro S, Minami M, Xing DJ and Ikejima T: Evodiamine, a constituent of evodiae fructus, induces anti-proliferating effects in tumor cells. Cancer Sci. 94:92–98. 2003. View Article : Google Scholar : PubMed/NCBI
10	Jiang J and Hu C: Evodiamine: A novel anti-cancer alkaloid from Evodia rutaecarpa. Molecules. 14:1852–1859. 2009. View Article : Google Scholar : PubMed/NCBI
11	Yang L, Liu X, Wu D, Zhang M, Ran G, Bi Y and Huang H: Growth inhibition and induction of apoptosis in SGC7901 human gastric cancer cells by evodiamine. Mol Med Rep. 9:1147–1152. 2014. View Article : Google Scholar : PubMed/NCBI
12	Chiou WF, Chou CJ, Shum AY and Chen CF: The vasorelaxant effect of evodiamine in rat isolated mesenteric arteries: Mode of action. Eur J Pharmacol. 215:277–283. 1992. View Article : Google Scholar : PubMed/NCBI
13	Hung PH, Lin LC, Wang GJ, Chen CF and Wang PS: Inhibitory effect of evodiamine on aldosterone release by Zona glomerulosa cells in male rats. Chin J Physiol. 44:53–57. 2001.PubMed/NCBI
14	Heo SK, Yun HJ, Yi HS, Noh EK and Park SD: Evodiamine and rutaecarpine inhibit migration by light via suppression of nadph oxidase activation. J Cell Biochem. 107:123–133. 2009. View Article : Google Scholar : PubMed/NCBI
15	Gordon D, Mohai LG and Schwartz SM: Induction of polyploidy in cultures of neonatal rat aortic smooth muscle cells. Circ Res. 59:633–644. 1986. View Article : Google Scholar : PubMed/NCBI
16	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) Method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
17	Sherr CJ: Cancer cell cycles. Science. 274:1672–1677. 1996. View Article : Google Scholar : PubMed/NCBI
18	Abukhdeir AM and Park BH: P21 and p27: Roles in carcinogenesis and drug resistance. Expert Rev Mol Med. 10:e192008. View Article : Google Scholar : PubMed/NCBI
19	Weiss RH, Joo A and Randour C: p21 (Waf1/Cip1) is an assembly factor required for platelet-derived growth factor-induced vascular smooth muscle cell proliferation. J Biol Chem. 275:10285–10290. 2000. View Article : Google Scholar : PubMed/NCBI
20	Fang C, Zhang J, Qi D, Fan X, Luo J, Liu L and Tan Q: Evodiamine induces G2/M arrest and apoptosis via mitochondrial and endoplasmic reticulum pathways in H446 and human small-cell lung cancer cells. PLoS One. 9:e1152042014. View Article : Google Scholar : PubMed/NCBI
21	Du J, Wang XF, Zhou QM, Zhang TL, Lu YY, Zhang H and Su SB: Evodiamine induces apoptosis and inhibits metastasis in MDAMB-231 human breast cancer cells in vitro and in vivo. Oncol Rep. 30:685–694. 2013.PubMed/NCBI
22	Rasul A, Yu B, Zhong L, Khan M, Yang H and Ma T: Cytotoxic effect of evodiamine in SGC-7901 human gastric adenocarcinoma cells via simultaneous induction of apoptosis and autophagy. Oncol Rep. 27:1481–1487. 2012.PubMed/NCBI
23	Yang J, Wu LJ, Tashino S, Onodera S and Ikejima T: Protein tyrosine kinase pathway-derived ROS/NO productions contribute to G2/M cell cycle arrest in evodiamine-treated human cervix carcinoma HeLa cells. Free Radic Res. 44:792–802. 2010. View Article : Google Scholar : PubMed/NCBI
24	Cuevas BD, Abell AN and Johnson GL: Role of mitogen-activated protein kinase kinase kinases in signal integration. Oncogene. 26:3159–3171. 2007. View Article : Google Scholar : PubMed/NCBI
25	Roux PP and Blenis J: ERK and p38 MAPK-activated protein kinases: A family of protein kinases with diverse biological functions. Microbiol Mol Biol Rev. 68:320–344. 2004. View Article : Google Scholar : PubMed/NCBI
26	Zhan Y, Kim S, Izumi Y, Izumiya Y, Nakao T, Miyazaki H and Iwao H: Role of JNK, p38 and ERK in platelet-derived growth factor-induced vascular proliferation, migration and gene expression. Arterioscler Thromb Vasc Biol. 23:795–801. 2003. View Article : Google Scholar : PubMed/NCBI
27	Yang L, Liu X, Wu D, Zhang M, Ran G, Bi Y and Huang H: Growth inhibition and induction of apoptosis in SGC7901 human gastric cancer cells by evodiamine. Mol Med Rep. 9:1147–1152. 2014. View Article : Google Scholar : PubMed/NCBI
28	Chen MC, Yu CH, Wang SW, Pu HF, Kan SF, Lin LC, Chi CW, Ho LL, Lee CH and Wang PS: Anti-proliferative effects of evodiamine on human thyroid cancer cell line ARO. J Cell Biochem. 110:1495–1503. 2010. View Article : Google Scholar : PubMed/NCBI
29	Yang J, Cai X, Lu W, Hu C, Xu X, Yu Q and Cao P: Evodiamine inhibits STAT3 signaling by inducing phosphatase shatterproof 1 in hepatocellular carcinoma cells. Cancer Lett. 328:243–251. 2013. View Article : Google Scholar : PubMed/NCBI
30	Yang J, Wu LJ, Tashiro S, Onodera S and Ikejima T: Nitric oxide activated by p38 and NF-kappaB facilitates apoptosis and cell cycle arrest under oxidative stress in evodiamine-treated human melanoma A375-S2 cells. Free Radic Res. 42:1–11. 2008. View Article : Google Scholar : PubMed/NCBI
31	Wang T, Wang Y, Kontani Y, Kobayashi Y, Sato Y, Mori N and Yamashita H: Evodiamine improves diet-induced obesity in a uncoupling protein-1-independent manner: Involvement of antiadipogenic mechanism and extracellularly regulated kinase/mitogen-activated protein kinase signaling. Endocrinology. 149:358–366. 2008. View Article : Google Scholar : PubMed/NCBI
32	Gao N, Zhang Z, Jiang BH and Shi X: Role of PI3K/AKT/mTOR signaling in the cell cycle progression of human prostate cancer. Biochem Biophys Res Commun. 310:1124–1132. 2003. View Article : Google Scholar : PubMed/NCBI
33	Roberts PJ and Der CJ: Targeting the Raf-MEK-ERK mitogen-activated protein kinase cascade for the treatment of cancer. Oncogene. 26:3291–3310. 2007. View Article : Google Scholar : PubMed/NCBI
34	Duronio V: The life of a cell: Apoptosis regulation by the PI3K/PKB pathway. Biochem J. 415:333–344. 2008. View Article : Google Scholar : PubMed/NCBI
35	Lim HJ, Lee S, Park JH, Lee KS, Choi HE, Chung KS, Lee HH and Park HY: PPAR delta agonist L-165041 inhibits rat vascular smooth muscle cell proliferation and migration via inhibition of cell cycle. Atherosclerosis. 202:446–454. 2009. View Article : Google Scholar : PubMed/NCBI
36	Conour JE, Graham WV and Gaskins HR: A combined in vitro/bioinformatic investigation of redox regulatory mechanisms governing cell cycle progression. Physiol Genomics. 18:196–205. 2004. View Article : Google Scholar : PubMed/NCBI
37	Pisoschi AM and Pop A: The role of antioxidants in the chemistry of oxidative stress: A review. Eur J Med Chem. 97:55–74. 2015. View Article : Google Scholar : PubMed/NCBI
38	Chen S, Ding Y, Tao W, Zhang W, Liang T and Liu C: Naringenin inhibits TNF-alpha induced VSMC proliferation and migration via induction of HO-1. Food Chem Toxicol. 50:3025–3031. 2012. View Article : Google Scholar : PubMed/NCBI