Anticancer effect of eupatilin on glioma cells through inhibition of the Notch-1 signaling pathway

Wang,Yawei; Hou,Hongwei; Li,Ming; Yang,Yang; Sun,Lan

doi:10.3892/mmr.2015.4671

Anticancer effect of eupatilin on glioma cells through inhibition of the Notch-1 signaling pathway

Authors:
- Yawei Wang
- Hongwei Hou
- Ming Li
- Yang Yang
- Lan Sun
View Affiliations

Affiliations: Department of Electromyography, Tianjin Hospital, Tianjin 300211, P.R. China, Department of Infection Control, Hebei Chest Hospital, Shijiazhuang, Hebei 050048, P.R. China, Basic Medical Institution, Shanghai Jiaotong University, Shanghai 200025, P.R. China, Department of Orthopedics, Tianjin Hospital, Tianjin 300211, P.R. China
Published online on: December 10, 2015 https://doi.org/10.3892/mmr.2015.4671
Pages: 1141-1146
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Eupatilin, one of the major flavonoids in Artemisia asiatica Nakai (Asteraceae), has been reported to possess antitumor properties. However, thus far there have been no reports regarding the effects of eupatilin on glioma. Therefore, in the current study the effects of eupatilin on glioma and the underlying molecular mechanism were explored. The effect of eupatilin on cell viability was detected by the MTT assay. Cell invasion and migration were performed with Transwell assays and cell apoptosis was determined by flow cytometric analysis. Notch‑1 knockdown cells were established by transfection with Notch‑1 small interfering RNA (siRNA). The expression levels of Notch‑1 were detected by quantitative reverse transcription‑polymerase chain reaction and western blotting. The results of the present study indicated that eupatilin exhibits an anticancer effect on glioma cells. Eupatilin inhibited proliferation, reduced cell invasion and migration, and promoted the apoptosis of glioma cells. Additionally, it suppressed Notch‑1 expression. Knockdown of Notch‑1 by siRNA contributed to the inhibitory effect of eupatilin on proliferation and invasion of glioma cells. In conclusion, eupatilin had an inhibitory effect on proliferation, invasion and migration, and promoted apoptosis of glioma cells through suppression of the Notch‑1 signaling pathway. Therefore, eupatilin may have potential as an effective agent for the treatment of glioma.

View Figures

View References

1	Jovčevska I, Kočevar N and Komel R: Glioma and glioblastoma - how much do we (not) know? Mol Clin Oncol. 1:935–941. 2013.
2	Partap S and Fisher PG: Update on new treatments and developments in childhood brain tumors. Curr Opin Pediatr. 19:670–674. 2007. View Article : Google Scholar : PubMed/NCBI
3	Van Meir EG, Hadjipanayis CG, Norden AD, Shu HK, Wen PY and Olson JJ: Exciting new advances in neuro-oncology: The avenue to a cure for malignant glioma. CA Cancer J Clin. 60:166–193. 2010. View Article : Google Scholar : PubMed/NCBI
4	Yaneva MP, Semerdjieva ML, Radev LR and Vlaikova MI: Postoperative chemo-radiotherapy with temodal in patients with glioblastoma multiforme - survival rates and prognostic factors. Folia Med (Plovdiv). 52:26–33. 2010.
5	Jung J, Ko SH, Yoo Y, Lee JY, Kim YJ, Choi SM, Kang KK, Yoon HJ, Kim H, Youn J and Kim JM: 5, 7-Dihydroxy-3,4,6-trimethoxyflavone inhibits intercellular adhesion molecule 1 and vascular cell adhesion molecule 1 via the Akt and nuclear factor-κB-dependent pathway, leading to suppression of adhesion of monocytes and eosinophils to bronchial epithelial cells. Immunology. 137:98–113. 2012. View Article : Google Scholar : PubMed/NCBI
6	Oh TY, Ahn GJ, Choi SM, Ahn BO and Kim WB: Increased susceptibility of ethanol-treated gastric mucosa to naproxen and its inhibition by DA-9601, an Artemisia asiatica extract. World J Gastroenterol. 11:7450–7456. 2005. View Article : Google Scholar
7	Choi EJ, Lee S, Chae JR, Lee H-S, Jun CD and Kim SH: Eupatilin inhibits lipopolysaccharide-induced expression of inflammatory mediators in macrophages. Life Sci. 88:1121–1126. 2011. View Article : Google Scholar : PubMed/NCBI
8	Oh TY, Lee JS, Ahn BO, Cho H, Kim WB, Kim YB, Surh YJ, Cho SW, Lee KM and Hahm KB: Oxidative stress is more important than acid in the pathogenesis of reflux oesophagitis in rats. Gut. 49:364–371. 2001. View Article : Google Scholar : PubMed/NCBI
9	Cheong JH, Hong SY, Zheng Y and Noh SH: Eupatilin inhibits gastric cancer cell growth by blocking STAT3-mediated VEGF expression. J Gastric Cancer. 11:16–22. 2011. View Article : Google Scholar : PubMed/NCBI
10	Park BB, Yoon J, Kim E, Choi J, Won Y, Choi J and Lee YY: Inhibitory effects of eupatilin on tumor invasion of human gastric cancer MKN-1 cells. Tumour Biol. 34:875–885. 2013. View Article : Google Scholar : PubMed/NCBI
11	Cho JH, Lee JG, Yang YI, Kim JH, Ahn JH, Baek NI, Lee KT and Choi J-H: Eupatilin, a dietary flavonoid, induces G2/M cell cycle arrest in human endometrial cancer cells. Food Chem Toxicol. 49:1737–1744. 2011. View Article : Google Scholar : PubMed/NCBI
12	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(−ΔΔC(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar
13	Côté MC, Lavoie JR, Houle F, Poirier A, Rousseau S and Huot J: Regulation of vascular endothelial growth factor-induced endothelial cell migration by LIM kinase 1-mediated phosphorylation of annexin 1. J Biol Chem. 285:8013–8021. 2010. View Article : Google Scholar : PubMed/NCBI
14	Teodorczyk M and Schmidt MH: Notching on cancer's door: Notch signaling in brain tumors. Front Oncol. 4:341–354. 2015. View Article : Google Scholar : PubMed/NCBI
15	Son JE, Lee E, Seo SG, Lee J, Kim JE, Kim J, Lee KW and Lee HJ: Eupatilin, a major flavonoid of Artemisia, attenuates aortic smooth muscle cell proliferation and migration by inhibiting PI3K, MKK3/6, and MKK4 activities. Planta Med. 79:1009–1016. 2013. View Article : Google Scholar : PubMed/NCBI
16	Kim DH, Na HK, Oh TY, Shin CY and Surh YJ: Eupatilin inhibits proliferation of ras-transformed human breast epithelial (MCF-10A-ras) cells. J Environ Pathol Toxicol Oncol. 24:251–259. 2005. View Article : Google Scholar
17	Kang N, Zhang J-H, Qiu F, Tashiro S, Onodera S and Ikejima T: Inhibition of EGFR signaling augments oridonin-induced apoptosis in human laryngeal cancer cells via enhancing oxidative stress coincident with activation of both the intrinsic and extrinsic apoptotic pathways. Cancer Lett. 294:147–158. 2010. View Article : Google Scholar : PubMed/NCBI
18	Strasser A, Cory S and Adams JM: Deciphering the rules of programmed cell death to improve therapy of cancer and other diseases. EMBO J. 30:3667–3683. 2011. View Article : Google Scholar : PubMed/NCBI
19	Seo HJ and Surh YJ: Eupatilin, a pharmacologically active flavone derived from Artemisia plants, induces apoptosis in human promyelocytic leukemia cells. Mutat Res. 496:191–198. 2001. View Article : Google Scholar : PubMed/NCBI
20	Kim MJ, Kim DH, Na HK, Oh TY, Shin CY and Surh Ph D Professor YJ: Eupatilin, a pharmacologically active flavone derived from Artemisia plants, induces apoptosis in human gastric cancer (AGS) cells. J Environ Pathol Toxicol Oncol. 24:261–269. 2005. View Article : Google Scholar
21	Ye QF, Zhang YC, Peng XQ, Long Z, Ming YZ and He LY: Silencing Notch-1 induces apoptosis and increases the chemosensitivity of prostate cancer cells to docetaxel through Bcl-2 and. Bax Oncol Lett. 3:879–884. 2012.
22	Kopan R and Ilagan MX: The canonical Notch signaling pathway: Unfolding the activation mechanism. Cell. 137:216–233. 2009. View Article : Google Scholar : PubMed/NCBI
23	Joutel A and Tournier-Lasserve E: Notch signalling pathway and human diseases. Semin Cell Dev Biol. 9:619–625. 1998. View Article : Google Scholar
24	Zheng Q, Qin H, Zhang H, Li J, Hou L, Wang H, Zhang X, Zhang S, Feng L, Liang Y, et al: Notch signaling inhibits growth of the human lung adenocarcinoma cell line A549. Oncol Rep. 17:847–852. 2007.PubMed/NCBI
25	Wang M, Xue L, Cao Q, Lin Y, Ding Y, Yang P and Che L: Expression of Notch1, Jagged1 and beta-catenin and their clinico-pathological significance in hepatocellular carcinoma. Neoplasma. 56:533–541. 2009. View Article : Google Scholar
26	Purow BW, Haque RM, Noel MW, Su Q, Burdick MJ, Lee J, Sundaresan T, Pastorino S, Park JK, Mikolaenko I, et al: Expression of Notch-1 and its ligands, Delta-like-1 and Jagged-1, is critical for glioma cell survival and proliferation. Cancer Res. 65:2353–2363. 2005. View Article : Google Scholar : PubMed/NCBI
27	Reedijk M, Odorcic S, Chang L, Zhang H, Miller N, McCready DR, Lockwood G and Egan SE: High-level coexpression of JAG1 and NOTCH1 is observed in human breast cancer and is associated with poor overall survival. Cancer Res. 65:8530–8537. 2005. View Article : Google Scholar : PubMed/NCBI
28	Wang J, Wang C, Meng Q, Li S, Sun X, Bo Y and Yao W: siRNA targeting Notch-1 decreases glioma stem cell proliferation and tumor growth. Mol Biol Rep. 39:2497–2503. 2012. View Article : Google Scholar
29	Xing ZY, Sun LG and Guo WJ: Elevated expression of Notch-1 and EGFR induced apoptosis in glioblastoma multiforme patients. Clin Neurol Neurosurg. 131:54–58. 2015. View Article : Google Scholar : PubMed/NCBI
30	Zhou ZD, Kumari U, Xiao ZC and Tan EK: Notch as a molecular switch in neural stem cells. IUBMB Life. 62:618–623. 2010. View Article : Google Scholar : PubMed/NCBI
31	Zhao N, Guo Y, Zhang M, Lin L and Zheng Z: Akt-mTOR signaling is involved in Notch-1-mediated glioma cell survival and proliferation. Oncol Rep. 23:1443–1447. 2010.PubMed/NCBI