Study the Effect of Sulforaphane on the Expression of CXCR4 and Snail in Breast Cancer Cells

Authors

  • Mehdi Bagheri1 1- Imam Hossein Center for Education, Research and Treatment, Shahroud University of Medical Sciences, Shahroud, Iran.
  • Mozhgan Fazli2 2- School of Medicine, Shahroud University of Medical Sciences, Shahroud, Iran.
  • Naghmeh Ahmadiankia2,3 3- Cancer Prevention Research Center, Shahroud University of Medical Sciences, Shahroud, Iran. orcid http://orcid.org/0000-0001-8309-4935

DOI:

https://doi.org/10.22100/jkh.v13i3.1953

Keywords:

Sulforaphane, Breast cancer, Metastasis, CXCR4، snail

Abstract

Introduction: Metastasis is known to be the primary cause of death in the majority of breast cancer patients. The transcription factor of snail and the signaling pathway of CXCR4/SDF1are one of the most important factors in the process of metastasis. Thus, targeting EMT and CXCR4/SDF1 pathway represents an important therapeutic strategy for preventing or treating breast cancer metastasis. Natural products due to their therapeutic activities constitute a common alternative for conventional treatments. Sulforaphane (SFN), an isothiocyanate found in cruciferous vegetables, exhibits anticancer properties. Accordingly, the aim of this study was to evaluate the effects of various concentrations of SFN on cell migration in breast cancer cells and also the expression of CXCR4 and snail which are important in EMT induction and metastasis.

Methods: MDA-MB-231 cells were treated with different concentrations of SFN. The effect of SFN on cell migration was evaluated using scratch assay, after 72 hours. Next, the effect of SFN on the expression of CXCR4 and snail were examined by real-time PCR.

Results: SFN significantly retarded the migration of MDA-MB-231 cells. High concentrations of SFN (40µM), reduced the expression of CXCR4; however, There was no significant changes in the expression of snail in none of studied concentrations.

Conclusion: According to the obtained results, SFN can be considered as a potential therapeutic agent to decrease breast cancer metastasis.

References

Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer 2015;136:E359-86. doi:10.1002/ijc.29210

DeSantis C, Ma J, Bryan L, Jemal A. Breast cancer statistics, 2013. CA Cancer J Clin 2014;64:52-62. doi:10.3322/caac.21203

Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin 2011;61:69-90. doi:10.3322/caac.20107

Tevaarwerk AJ, Gray RJ, Schneider BP, Smith ML, Wagner LI, Fetting JH, et al. Survival in patients with metastatic recurrent breast cancer after adjuvant chemotherapy: little evidence of improvement over the past 30 years. Cancer 2013;119:1140-8. doi:10.1002/cncr.27819

Chakrabarti R1, Hwang J, Andres Blanco M, Wei Y, Lukačišin M, Romano RA, et al. Elf5 inhibits the epithelial–mesenchymal transition in mammary gland development and breast cancer metastasis by transcriptionally repressing Snail2. Nat Cell Biol 2012;14:1212-22. doi:10.1038/ncb2607

Chambers AF, Groom AC, MacDonald IC. Dissemination and growth of cancer cells in metastatic sites. Nat Rev Cancer 2002;2:563-72. doi:10.1038/nrc865

Xu C, Zhao H, Chen H, Yao Q. CXCR4 in breast cancer: oncogenic role and therapeutic targeting. Drug Des Devel Ther 2015;9:4953-64. doi:10.2147/DDDT.S84932

Salvucci O, Yao L, Villalba S, Sajewicz A, Pittaluga S, Tosato G. Regulation of endothelial cell branching morphogenesis by endogenous chemokine stromal-derived factor-1. Blood 2002;99:2703-11.

Dewan MZ, Ahmed S, Iwasaki Y, Ohba K, Toi M, Yamamoto N. Stromal cell-derived factor-1 and CXCR4 receptor interaction in tumor growth and metastasis of breast cancer. Biomed Pharmacother 2006;60:273-6. doi:10.1016/j.biopha.2006.06.004

Müller A, Homey B, Soto H, Ge N, Catron D, Buchanan ME, et al. Involvement of chemokine receptors in breast cancer metastasis. Nature 2001;410:50-6. doi:10.1038/35065016

Radisky DC. Epithelial-mesenchymal transition. J Cell Sci 2005;118:4325-6. doi:10.1242/jcs.02552

Thiery JP. Epithelial–mesenchymal transitions in tumour progression. Nat Rev Cancer 2002;2:442-54. doi:10.1038/nrc822

Blanco MJ, Moreno-Bueno G, Sarrio D, Locascio A, Cano A, Palacios J, et al. Correlation of Snail expression with histological grade and lymph node status in breast carcinomas. Oncogene 2002;21:3241-6. doi:10.1038/sj.onc.1205416

Darash-Yahana M, Pikarsky E, Abramovitch R, Zeira E, Pal B, Karplus R, et al. Role of high expression levels of CXCR4 in tumor growth, vascularization, and metastasis. FASEB J 2004;18:1240-2. doi:10.1096/fj.03-0935fje

Olmeda D, Jorda M, Peinado H, Fabra A, Cano A. Snail silencing effectively suppresses tumour growth and invasiveness. Oncogene 2007;26:1862-74. doi:10.1038/sj.onc.1209997

Coseri S. Natural products and their analogues as efficient anticancer drugs. Mini Rev Med Chem 2009;9:560-71.

Luo J, Solimini NL, Elledge SJ. Principles of cancer therapy: oncogene and non-oncogene addiction. Cell 2009;136:823-37. doi:10.1016/j.cell.2009.02.024

Kensler TW, Egner PA, Agyeman AS, Visvanathan K, Groopman JD, Chen JG, et al. Keap1-nrf2 signaling: a target for cancer prevention by sulforaphane. Top Curr Chem 2013;329:163-77. doi:10.1007/128_2012_339

Lenzi M, Fimognari C, Hrelia P. Sulforaphane as a promising molecule for fighting cancer. Cancer Treat Res 2014;159:207-23. doi:10.1007/978-3-642-38007-5_12

Di Pasqua AJ, Hong C, Wu MY, McCracken E, Wang X, Mi L, et al. Sensitization of non-small cell lung cancer cells to cisplatin by naturally occurring isothiocyanates. Chem Res Toxicol 2010;23:1307-9. doi:10.1021/tx100187f

Vyas AR, Singh SV. Functional relevance of D, L-sulforaphane-mediated induction of vimentin and plasminogen activator inhibitor-1 in human prostate cancer cells. Eur J Nutr 2014;53:843-52. doi:10.1007/s00394-013-0588-5

Tang L, Zirpoli GR, Guru K, Moysich KB, Zhang Y, Ambrosone CB, et al. Consumption of raw cruciferous vegetables is inversely associated with bladder cancer risk. Cancer Epidemiol Biomarkers Prev 2008;17:938-44. doi:10.1158/1055-9965.EPI-07-2502

Li W, Khor TO, Xu C, Shen G, Jeong WS, Yu S, et al. Activation of Nrf2-antioxidant signaling attenuates NFκB-inflammatory response and elicits apoptosis. Biochem Pharmacol 2008;76:1485-9. doi:10.1016/j.bcp.2008.07.017

Kensler TW, Egner PA, Agyeman AS, Visvanathan K, Groopman JD, Chen JG, et al. Keap1–nrf2 signaling: a target for cancer prevention by sulforaphane. Top Curr Chem 2013;329:163-77. doi:10.1007/128_2012_339

Wang L, Tian Z, Yang Q, Li H, Guan H, Shi B, et al. Sulforaphane inhibits thyroid cancer cell growth and invasiveness through the reactive oxygen species-dependent pathway. Oncotarget 2015;6:25917-31. doi:10.18632/oncotarget.4542

Balkwill F. Cancer and the chemokine network. Nat Rev Cancer 2004;4:540-50. doi:10.1038/nrc1388

Kim B, Park B. Baohuoside I suppresses invasion of cervical and breast cancer cells through the downregulation of CXCR4 chemokine receptor expression. Biochemistry 2014;53:7562-9. doi:10.1021/bi5011927

Chen XP, Qian LL, Jiang H, Chen JH. Ginsenoside Rg3 inhibits CXCR 4 expression and related migrations in a breast cancer cell line. Int J Clin Oncol 2011;16:519-23. doi:10.1007/s10147-011-0222-6

Hirbe AC, Morgan EA, Weilbaecher KN. The CXCR4/SDF-1 chemokine axis: a potential therapeutic target for bone metastases? Curr Pharm Des 2010;16:1284-90.

Hu CT, Wu JR, Chang TY, Cheng CC, Wu WS. The transcriptional factor Snail simultaneously triggers cell cycle arrest and migration of human hepatoma HepG2. J Biomed Sci 2008;15:343-55. doi:10.1007/s11373-007-9230-y

Chen J, Chang H, Peng X, Gu Y, Yi L, Zhang Q, et al. 3, 6-dihydroxyflavone suppresses the epithelial-mesenchymal transition in breast cancer cells by inhibiting the Notch signaling pathway. Sci Rep 2016;6:28858. doi:10.1038/srep28858

Published

2018-11-19

Issue

Section

Original Article(s)

How to Cite

Study the Effect of Sulforaphane on the Expression of CXCR4 and Snail in Breast Cancer Cells. (2018). Knowledge and Health in Basic Medical Sciences, 13(3), 8-13. https://doi.org/10.22100/jkh.v13i3.1953

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