Browse > Article

Inhibitory Effects of Harmine on Migration and Invasion of Human Breast Cancer Cells by Regulating Notch Signaling  

Yun, Jieun (Department of Pharmaceutical Engineering, Cheongju University)
Publication Information
Korean Journal of Pharmacognosy / v.49, no.4, 2018 , pp. 285-290 More about this Journal
Abstract
Harmine, a beta-carboline alkaloid isolated from the seeds of Peganum harmala has been reported as a promising drug candidate for cancer therapy. However, the effect of harmine on breast cancer remains still unclear. In this study, the effect of harmine on the cell proliferation, migration, and invasion of breast cancer MDA-MB231 cells and the underlying mechanism were investigated. The results indicated that harmine inhibited the proliferation MDA-MB231 cells in a dose-dependent manner and markedly suppressed migration and invasion of MDA-MB231 cells. The mechanism involved in part through Notch signaling. The Notch activity was significantly inhibited by harmine treatment and harmine suppressed the expression of Jagged1 which is a key ligand to activate Notch signaling. These findings suggest a novel mechanism of harmine on anti-cancer activity and harmine may act as a potential therapeutic drug for breast cancer treatment.
Keywords
Harmine; Peganum harmala; Breast cancer; Invasion; Notch signaling;
Citations & Related Records
연도 인용수 순위
  • Reference
1 Armstrong, F., Brunet de la Grange, P., Gerby, B., Rouyez, M. C., Calvo, J., Fontenay, M., Boissel, N., Dombret, H., Baruchel A., Landman-Parker, J., Romeo, P. H., Ballerini, P. and Pflumio, F. (2009) NOTCH is a key regulator of human T-cell acute leukemia initiating cell activity. Blood 113: 1730-1740.   DOI
2 Garcia, A. and Kandel, J. J. (2012) Notch: A key regulator of tumor angiogenesis and metastasis. Histol. Histopathol. 27: 151-156.
3 Shah, D., Wyatt, D., Baker, A. T., Simms, P., Peiffer, D. S., Fernandez, M., Rakha, E., Green, A., Filipovic, A., Miele, L. and Osipo, C. (2018) Inhibition of HER2 increases JAGGED1-dependent breast cancer stem cells: role for membrane JAGGED1. Clin. Cancer Res. 24: 4566-4578.   DOI
4 Sethi, N., Dai, X., Winter, C. G. and Kang, Y. (2011) Tumorderived JAGGED1 promotes osteolytic bone metastasis of breast cancer by engaging notch signaling in bone cells. Cancer Cell 19: 192-205.   DOI
5 Espinoza, I. and Miele, L. (2013) Deadly crosstalk: Notch signaling at the intersection of EMT and cancer stem cells. Cancer Lett. 341: 41-45.   DOI
6 Espinoza, I., Pochampally, R., Xing, F., Watabe, K. and Miele, L. (2013) Notch signaling: targeting cancer stem cells and epithelial-to-mesenchymal transition. Onco. Targets Ther. 6: 1249-1259.
7 Shao, S., Zhao, X., Zhang, X., Luo, M., Zuo, X., Huang, S., Wang, Y., Gu, S. and Zhao X. (2015) Notch1 signaling regulates the epithelial-mesenchymal transition and invasion of breast cancer in a Slug-dependent manner. Mol. Cancer 14: 28.   DOI
8 Siegel, R. L., Miller, K. D. and Jemal, A. (2017) Cancer statistics. CA Cancer J. Clin. 67: 7-30.   DOI
9 Scully, O. J., Bay, B. -H., Yip, G. and Yu, Y. (2012) Breast cancer metastasis. Cancer Genomics and Proteomics 9: 311-320.
10 Massague, J. (2007) Sorting out breast-cancer gene signatures. N. Engl. J. Med. 356: 294-297.   DOI
11 Geng, X., Ren, Y., Wang, F., Tian, D., Yao, X., Zhang, Y. and Tang, J. (2018) Harmines inhibit cancer cell growth through coordinated activation of apoptosis and inhibition of autophagy. Biochem. Biophys. Res. Commun. 498: 99-104.   DOI
12 Daoud, A., Song, J., Xiao, F. and Shang, J. (2014) B-9-3, a novel ${\beta}$-carboline derivative exhibits anti-cancer activity via induction of apoptosis and inhibition of cell migration in vitro. Eur. J. Pharmacol. 724:219-230.   DOI
13 Gao, J., Zhu, H., Wan, H., Zou, X., Ma, X. and Gao, G. (2017) Harmine suppresses the proliferation and migration of human ovarian cancer cells through inhibiting ERK/CREB pathway Oncol. Rep. 38: 2927-2934.   DOI
14 Yu, X. J., Sun, K., Tang, X. H., Zhou, C. J., Sun, H., Yan, Z., Fang, L., Wu, H. W., Xie, Y. K. and Gu, B. (2016) Harmine combined with paclitaxel inhibits tumor proliferation and induces apoptosis through down-regulation of cyclooxygenase-2 expression in gastric cancer. Oncol. Lett. 12: 983-988.   DOI
15 Ruan, S., Jia, F. and Li, J. (2017) Potential antitumor effect of harmine in the treatment of thyroid cancer. Evid. Based Complement Alternat. Med. 2017: 9402615.
16 Yochum, Z. A., Cades, J., Mazzacurati, L., Neumann, N. M., Khetarpal, S. K., Chatterjee, S., Wang, H., Attar, M. A., Huang, E. H., Chatley, S. N., Nugent, K., Somasundaram, A., Engh, J. A., Ewald, A. J., Cho, Y. J., Rudin, C. M., Tran, P. T. and Burns, T. F. (2017) A first-in-class TWIST1 inhibitor with activity in oncogene-driven lung cancer. Mol. Cancer Res. 15: 1764-1776.   DOI
17 Hashemi Sheikh Shabani, S., Seyed Hasan Tehrani, S., Rabiei, Z., Tahmasebi Enferadi, S. and Vannozzi, G. P. (2015) Peganum harmala L.'s anti-growth effect on a breast cancer cell line. Biotechnol. Rep. (Amst) 8: 138-143.   DOI
18 Borggrefe, T. and Oswald, F. (2009) The Notch signaling pathway: transcriptional regulation at Notch target genes. Cell Mol. Life Sci. 66: 1631-1646.   DOI
19 Miele, L. (2016) Notch signaling. Clinical Cancer Research 12: 1074-1079.