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Curcumin inhibits metastatic progression of breast cancer cell through suppression of urokinase-type plasminogen activator by NF-kappa B signaling pathways

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Abstract

Curcumin (1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione), is extracted from the plant Curcuma longa. It was recently reported for its anticancer effect on several types of cancer cells in vitro however, the molecular mechanisms of this anticancer effect are not fully understood. In the present study, we evaluated the effects of curcumin on human mammary epithelial carcinoma MCF-7 cells. Cells were treated with curcumin and examined for cell viability by MTT assay. The cells invasion was demonstrated by transwell assay. The binding activity of NF-κB to DNA was examined in nuclear extracts using Trans-AM NF-κB ELISA kit. Western blot was performed to detect the effect of curcumin on the expression of uPA. Our results showed that curcumin dose-dependently inhibited (P < 0.05) the proliferation of MCF-7 cells. Meanwhile, the adhesion and invasion ability of MCF-7 cells were sharply inhibited when treated with different concentrations of curcumin. Curcumin also significantly decreased (P < 0.05) the expression of uPA and NF-κB DNA binding activity, respectively. It is concluded that curcumin inhibits the adhesion and invasion of MCF-7 cells through down-regulating the protein expression of uPA via of NF-κB activation. Accordingly, the therapeutic potential of curcumin for breast cancer deserves further study.

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References

  1. Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ (2009) Cancer statistics, 2009. CA Cancer J Clin 59:225–249

    Article  PubMed  Google Scholar 

  2. Jovanovic J, Rønneberg JA, Tost J, Kristensen V (2010) The epigenetics of breast cancer. Mol Oncol 4:242–254

    Article  PubMed  CAS  Google Scholar 

  3. Wickerham DL (2010) Breast cancer chemoprevention: progress and controversy. Surg Oncol Clin N Am 19:463–473

    Article  PubMed  Google Scholar 

  4. Hatcher H, Planalp R, Cho J, Torti FM, Torti SV (2008) Curcumin: from ancient medicine to current clinical trials. Cell Mol Life Sci 65:1631–1652

    Article  PubMed  CAS  Google Scholar 

  5. Kawamori T, Lubet R, Steele VE, Kelloff GJ, Kaskey RB, Rao CV, Reddy BS (1999) Chemopreventive effect of curcumin, a naturally occurring anti-inflammatory agent, during the promotion/progression stages of colon cancer. Cancer Res 59:597–601

    PubMed  CAS  Google Scholar 

  6. Shi M, Cai Q, Yao L, Mao Y, Ming Y, Ouyang G (2006) Antiproliferation and apoptosis induced by curcumin in human ovarian cancer cells. Cell Biol Int 30:221–226

    Article  PubMed  CAS  Google Scholar 

  7. Johnson SM, Gulhati P, Arrieta I, Wang X, Uchida T, Gao T, Evers BM (2009) Curcumin inhibits proliferation of colorectal carcinoma by modulating Akt/mTOR signaling. Anticancer Res 29:3185–3190

    PubMed  CAS  Google Scholar 

  8. Kim SY, Jung SH, Kim HS (2005) Curcumin is a potent broad spectrum inhibitor of matrix metalloproteinase gene expression in human astroglioma cells. Biochem Biophys Res Commun 337:510–516

    Article  PubMed  CAS  Google Scholar 

  9. Kunnumakkara AB, Anand P, Aggarwal BB (2008) Curcumin inhibits proliferation, invasion, angiogenesis and metastasis of different cancers through interaction with multiple cell signaling proteins. Cancer Lett 269:199–225

    Article  PubMed  CAS  Google Scholar 

  10. Mukhopadhyay A, Banerjee S, Stafford LJ, Xia C, Liu M, Aggarwal BB (2002) Curcumin-induced suppression of cell proliferation correlates with down-regulation of cyclin D1 expression and CDK4-mediated retinoblastoma protein phosphorylation. Oncogene 21:8852–8861

    Article  PubMed  CAS  Google Scholar 

  11. Brooks SA, Lomax-Browne HJ, Carter TM, Kinch CE, Hall DM (2010) Molecular interactions in cancer cell metastasis. Acta Histochem 112:3–25

    Article  PubMed  CAS  Google Scholar 

  12. Roy R, Yang J, Moses MA (2009) Matrix metalloproteinases as novel biomarkers and potential therapeutic targets in human cancer. J Clin Oncol 27:5287–5297

    Article  PubMed  CAS  Google Scholar 

  13. Raghu H, Sodadasu PK, Malla RR, Gondi CS, Estes N, Rao JS (2010) Localization of uPAR and MMP-9 in lipid rafts is critical for migration, invasion and angiogenesis in human breast cancer cells. BMC Cancer 10:647

    Article  PubMed  CAS  Google Scholar 

  14. Mazar AP, Henkin J, Goldfarb RH (1999) The urokinase plasminogen activator system in cancer: implications for tumor angiogenesis and metastasis. Angiogenesis 3:15–32

    Article  PubMed  CAS  Google Scholar 

  15. Chandrasekar N, Mohanam S, Gujrati M, Olivero WC, Dinh DH, Rao JS (2003) Downregulation of uPA inhibits migration and PI3k/Akt signaling in glioblastoma cells. Oncogene 22:392–400

    Article  PubMed  CAS  Google Scholar 

  16. Huang S, Pettaway CA, Uehara H, Bucana CD, Fidler IJ (2001) Blockade of NF-κB 12 activity in human prostate cancer cells is associated with suppression of angiogenesis, invasion, and metastasis. Oncogene 20:4188–4197

    Article  PubMed  CAS  Google Scholar 

  17. Siwak DR, Shishodia S, Aggarwal BB, Kurzrock R (2005) Curcumin-induced antiproliferative and proapoptotic effects in melanoma cells are associated with suppression of the InB kinase and nuclear factor κB activity and are independent of the B-raf/Mitogen activated/extracellular signal-regulated protein kinase pathway and the AKT pathway. Cancer 104:879–890

    Article  PubMed  CAS  Google Scholar 

  18. Cai XZ, Wang J, Li XD, Wang GL, Liu FN, Cheng MS, Li F (2009) Curcumin suppresses proliferation and invasion in human gastric cancer cells by downregulation of PAK1 activity and cyclin D1 expression. Cancer Biol Ther 8:1360–1368

    Article  PubMed  CAS  Google Scholar 

  19. Aravindan N, Madhusoodhanan R, Ahmad S, Johnson D, Herman TS (2008) Curcumin inhibits NFkappaB mediated radioprotection and modulate apoptosis related genes in human neuroblastoma cells. Cancer Biol Ther 7:569–576

    PubMed  CAS  Google Scholar 

  20. Visse R, Nagase H (2003) Matrix metalloproteinases and tissue inhibitors of metalloproteinases: structure, function, and biochemistry. Circ Res 92:827–839

    Article  PubMed  CAS  Google Scholar 

  21. Andreasen PA, Egelund R, Petersen HH (2000) The plasminogen activation system in tumor growth, invasion, and metastasis. Cell Mol Life Sci 57:25–40

    Article  PubMed  CAS  Google Scholar 

  22. Crowley CW, Cohen RL, Lucas BK, Liu G, Shuman MA, Levinson AD (1993) Prevention of metastasis by inhibition of the urokinase receptor. Proc Natl Acad Sci USA 90:5021–5025

    Article  PubMed  CAS  Google Scholar 

  23. Andreasen PA, Kjøller L, Christensen L, Duffy MJ (1997) The urokinase-type plasminogen activator system in cancer metastasis: a review. Int J Cancer 72:1–22

    Article  PubMed  CAS  Google Scholar 

  24. Ossowski L, Aguirre-Ghiso JA (2000) Urokinase receptor and integrin partnership: 13 coordination of signaling for cell adhesion, migration and growth. Curr Opin Cell Biol 12:613–620

    Article  PubMed  CAS  Google Scholar 

  25. Yebra M, Goretzki L, Pfeifer M, Mueller BM (1999) Urokinase-type plasminogen activator binding to its receptor stimulates tumor cell migration by enhancing integrin-mediated signal transduction. Exp Cell Res 250:231–240

    Article  PubMed  CAS  Google Scholar 

  26. Sandur SK, Deorukhkar A, Pandey MK, Pabon AM, Shentu S, Guha S, Aggarwal BB, Krishnan S (2009) Curcumin modulates the radiosensitivity of colorectal cancer cells by suppressing constitutive and inducible NF kappaB activity. Int J Radiat Oncol Biol Phys 75:534–542

    Article  PubMed  CAS  Google Scholar 

  27. Hartojo W, Silvers AL, Thomas DG, Seder CW, Lin L, Rao H, Wang Z, Greenson JK, Giordano TJ, Orringer MB, Rehemtulla A, Bhojani MS, Beer DG, Chang AC (2010) Curcumin promotes apoptosis, increases chemosensitivity, and inhibits nuclear factor kappaB in esophageal adenocarcinoma. Transl Oncol 3:99–108

    PubMed  Google Scholar 

  28. Cheng JC, Chou CH, Kuo ML, Hsieh CY (2006) Radiation-enhanced hepatocellular carcinoma cell invasion with MMP-9 expression through PI3K/Akt/NF-kappaB signal transduction pathway. Oncogene 25:7009–7018

    Article  PubMed  CAS  Google Scholar 

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The authors declare that they have no competing interests.

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Authors and Affiliations

  1. Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, People’s Republic of China

    Hong Zong, Feng Wang, Qing-xia Fan & Liu-xing Wang

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  1. Hong Zong
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  2. Feng Wang
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  3. Qing-xia Fan
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  4. Liu-xing Wang
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Correspondence to Liu-xing Wang.

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Hong Zong and Feng Wang contributed equally to this work.

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Zong, H., Wang, F., Fan, Qx. et al. Curcumin inhibits metastatic progression of breast cancer cell through suppression of urokinase-type plasminogen activator by NF-kappa B signaling pathways. Mol Biol Rep 39, 4803–4808 (2012). https://doi.org/10.1007/s11033-011-1273-5

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  • DOI: https://doi.org/10.1007/s11033-011-1273-5

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