Gastric cancer represents a major cause of cancer-related death worldwide. Although various tactics and anti-tumor drugs have been used to improve curative effects, five-year survival rate of lung cancer patients remains poor. Evodiamine, a sophora alkaloid, has been demonstrated to exert antitumor effects on many types of cancer. However, the molecular mechanism of evodiamine against gastric cancer has not been clearly elucidated. In this study, we investigated the anti-tumor activity and the underlying mechanisms of EVO on gastric cancer cells, and found that it significantly inhibited the proliferation of BGC-823 and SGC-7901 cells by inducing cell cycle arrest at G2/M phase and cell apoptosis in a dose- and time-dependent manner. Its molecular mechanism may be that it reduces the expression of cell cycle- promoting protein Cdc25C and promotes the expression of cell cycle inhibitor p53, as well as prompts the activity of caspases pathways, such as the expression level of cleaved caspase-3 and cleaved caspase-8; cleaved caspase-9 and cleaved PARP-1 are up-regulated, treated with EVO (10 μM) at different points in time (0, 3, 6, 9, 12, 24 h). Collectively, our data demonstrated that EVO was a potential anti-tumor agent against gastric cancer.
Cite this paper
Zhang, H. , Guo, Y. , Ge, K. and Wang, Y. (2019). Evodiamine Inhibits the Proliferation of BGC-823 and SGC-7901 Cells by Inducing Cell Cycle Arrest and Apoptosis in Gastric Cancer. Open Access Library Journal, 6, e5217. doi: http://dx.doi.org/10.4236/oalib.1105217.
Ferlay, J., Soerjomataram, I., Dikshit, R., et al. (2015) Cancer Incidence and Mortality Worldwide: Sources, Methods and Major Patterns in GLOBOCAN 2012. International Journal of Cancer, 136, E359-E386. https://doi.org/10.1002/ijc.29210
Chen, W.Q., Zheng, R.S., Peter, D., et al. (2016) Cancer Statistics in China, 2015. CA: A Cancer Journal for Clinicians, 2, 115-132. https://doi.org/10.3322/caac.21338
Mihmanli, M., Ilhan, E., Idiz, U.O., et al. (2016) Recent Developments and Innovations in Gastric Cancer. World Journal of Gastroenterology, 22, 4307-4320. https://doi.org/10.3748/wjg.v22.i17.4307
Feng, Y., Wu, C.Y. and Li, J. (2017) Research Progress on the Advantages and Possible Mechanisms of Traditional Chinese Medicine in the Treatment of Gastric Cancer. Liaoning Journal of Traditional Chinese Medicine, 44, 200-203.
Zhang, Q.R., Zhou, Z.Y., Pan, Z.H., et al. (2018) Evodiamine Inhibits the Growth of Huh7 Cells and Enhances the Sensitivity of Cells to TRAIL. Chinese Journal of Pathophysiology, 34, 212-217.
Yang, F., Shi, L., Liang, T., et al. (2017) Anti-Tumor Effect of Evodiamine by Inducing Akt-Mediated Apoptosis in Hepatocellular Carcinoma. Biochemical and Biophysical Research Communications, 485, 54-61. https://doi.org/10.1016/j.bbrc.2017.02.017
Han, S., Woo, J.K., Jung, Y., et al. (2016) Evodiamine Selectively Targets Cancer Stem-Like Cells through the p53-p21-Rb Pathway. Biochemical and Biophysical Research Communications, 469, 1153-1158. https://doi.org/10.1016/j.bbrc.2015.12.066
Huang, J., Chen, Z.H., Ren, C.M., et al. (2015) Antiproliferation Effect of Evodiamine in Human Colon Cancer Cells Is Associated with IGF-1/HIF-1α Downregulation. Oncology Reports, 34, 3203-3211. https://doi.org/10.3892/or.2015.4309
Mohan, V., Agarwal, R. and Singh, R.P. (2016) A Novel Alkaloid, Evodiamine Causes Nuclear Localization of Cytochrome-c and Induces Apoptosis Independent of p53 in Human Lung Cancer cells. Biochemical and Biophysical Research Communications, 477, 1065-1071. https://doi.org/10.1016/j.bbrc.2016.07.037
Zhang, Y., Zhang, Q.H., Wu, L.J., et al. (2004) Cell Cycle Arrest in the Induction of Apoptosis in Mouse Fibrosarcoma L929 Cells. Chinese Journal of Integrated Traditional and Western Medicine, 24, 169-172.
Bai, X., Meng, H., Ma, L., et al. (2015) Inhibitory Effects of Evodiamine on Human Osteosarcoma Cell Proliferation and Apoptosis. Oncology Letters, 9, 801-805. https://doi.org/10.3892/ol.2014.2791
Tian, X.L., Zhang, W. and Wang, X.L. (2011) Study on the Effect of Evodiamine on Human Gastric Adenocarcinoma Cell Line SGC-7901. Journal of Beijing University of Traditional Chinese Medicine, 34, 115-118.
Sanchez, I. and Dynlacht, B.D. (2005) New Insights into Cyclins, CDKs, and Cell Cycle Control. Seminars in Cell and Developmental Biology, 16, 311-321. https://doi.org/10.1016/j.semcdb.2005.02.007
Peter, M., Le Peuch, C., Labbé, J.C., et al. (2002) Initial Activation of Cyclin-B1-cdc2 Kinase Requires Phos-phorylation of Cyclin B1. EMBO Reports, 3, 551-556. https://doi.org/10.1093/embo-reports/kvf111
Chien, C.C., Wu, M.S., Shen, S.C., et al. (2014) Activation of JNK Contributes to Evodiamine-Induced Apoptosis and G2/M Arrest in Human Colorectal Carcinoma Cells: A Structure-Activity Study of Evodiamine. PLoS ONE, 9, e99729. https://doi.org/10.1371/journal.pone.0099729
Lu, X., Liu, D.A. And Xu, Y. (2013) The Gain of Function of p53 Cancer Mutant in Promoting Mammary Tumorigenesis. Oncogene, 32, 2900-2906. https://doi.org/10.1038/onc.2012.299
Yin, X., Zhang, R., Feng, C., et al. (2014) Diallyl Disulfide Induces G2/M Arrest and Promotes Apoptosis through the p53/p21 and MEK-ERK Pathways in Human Esophageal Squamous Cell Carcinoma. Oncology Reports, 32, 1748-1756. https://doi.org/10.3892/or.2014.3361
Wawryk-Gawda, E., Chylińska-Wrzos, P., Lis-Sochocka, M., et al. (2014) P53 Protein in Proliferation, Repair and Apoptosis of Cells. Protoplasma, 251, 525-533. https://doi.org/10.1007/s00709-013-0548-1
St. Clair, S., Giono, L., Varmeh-Ziaie, S., et al. (2004) DNA Damage-Induced Downregulation of Cdc25C Is Mediated by p53 via Two Independent Mechanisms: One Involves Direct Binding to the cdc25C Promoter. Molecular Cell, 16, 725-736. https://doi.org/10.1016/j.molcel.2004.11.002
Fu, Z., Han, X., Du, J., et al. (2018) Euphorbialunulata Extract Acts on Multidrug Resistant Gastric Cancer Cells to Inhibit Cell Proliferation, Migration and Invasion, Arrest Cell Cycle Progression, and Induce Apoptosis. Journal of Ethnopharmacology, 212, 8-17. https://doi.org/10.1016/j.jep.2017.08.014
Xu, Y., Gao, C.C., Pan, Z.G., et al. (2018) Irigenin Sensitizes TRAIL-Induced Apoptosis via Enhancing Pro-Apoptotic Molecules in Gastric Cancer Cells. Biochemical and Biophysical Research Communications, 496, 998-1005. https://doi.org/10.1016/j.bbrc.2018.01.003
