Asian Pacific Journal of Cancer Prevention

Asian Pacific Journal of Cancer Prevention (아시아태평양암예방학회)
권호 표지
DOI QR코드

DOI QR Code

Curcumin Effect on MMPs and TIMPs Genes in a Breast Cancer Cell Line

  • Hassan, Zeinab Korany (Department of Zoology, Center for Scientific and Medical Female Colleges, King Saud University) ;
  • Daghestani, Maha Hassan (Department of Zoology, Center for Scientific and Medical Female Colleges, King Saud University)
  • Published : 2012.07.31
Download PDF
⟨ Previous Next ⟩

Abstract

Curcumin (CM) possesses anti-cancer activity against a variety of tumors. Matrix metalloproteinases (MMPs) play an important role in remodeling the extracellular matrix and their activities are regulated by tissue inhibitor of metalloproteinases (TIMPs) family. Control of MMP and TIMP activity are now of great significance. In this study, the effect of CM is investigated on metastatic MMPs and anti-metastatic TIMPs genes on MDA breast cancer cells cultured in a mixture of DMEM and Ham's F12 medium and treated with different concentrations of CM (10, 20 and $40{\mu}M$ for various lengths of time. Reverse transcription followed by quantitative real time PCR was used to detect the gene expression levels of MMPs and TIMPs in CM-treated versus untreated cases and the data were analyzed by one-way ANOVA. At high concentrations of curcumin, TIMP-1, -2, -3 and -4 genes were up-regulated after 48 hours of treatment, their over-expression being accompanied by down-regulation of MMP-2 and MMP-9 gene expression levels in a concentration- and time-dependent manner. These results suggest that curcumin plays a role in regulating cell metastasis by inhibiting MMP-2 and MMP-9 and up-regulating TIMP1 and TIMP4 gene expression in breast cancer cells.

Keywords

References

  1. Aggarwal B B, Banerjee S, Bharadwaj U, et al (2007). Curcumin induces the degradation of cyclin E expression through ubiquitin-dependent pathway and up-regulates cyclin-dependent kinase inhibitors p21 and p27 in multiple human tumor cell lines. Biochem Pharmacol, 73, 1024-32. https://doi.org/10.1016/j.bcp.2006.12.010
  2. Baker E A, Bergin F G, Leaper D J (2000). Matrix metalloproteinases, their tissue inhibitors and colorectal cancer staging. Br J Surg, 87, 1215-21. https://doi.org/10.1046/j.1365-2168.2000.01531.x
  3. Baker E A, Stephenson T J, Reed M W, Brown N J (2002). Expression of proteinases and inhibitors in human breast cancer progression and survival. Mol Pathol, 55, 300-4. https://doi.org/10.1136/mp.55.5.300
  4. Bica C G, Da Silva L L, Toscani N V, et al (2010). Polymorphism (ALA16VAL) correlates with regional lymph node status in breast cancer. Cancer Genet Cytogenet, 196, 153-8. https://doi.org/10.1016/j.cancergencyto.2009.09.011
  5. Brummer O, Athar S, Riethdorf L, et al (1999). Matrix-metalloproteinases 1, 2, and 3 and their tissue inhibitors 1 and 2 in benign and malignant breast lesions: an in situ hybridization study. Virchows Arch, 435, 566-73. https://doi.org/10.1007/s004280050442
  6. Buck T B, Yoshiji H, Harris S R, Bunce O R, Thorgeirsson U P (1999). The effects of sustained elevated levels of circulating tissue inhibitor of metalloproteinases-1 on the development of breast cancer in mice. Ann N Y Acad Sci, 878, 732-5. https://doi.org/10.1111/j.1749-6632.1999.tb07775.x
  7. Chen A, Xu J, Johnson A C (2006). Curcumin inhibits human colon cancer cell growth by suppressing gene expression of epidermal growth factor receptor through reducing the activity of the transcription factor Egr-1. Oncogene, 25, 278-87.
  8. Chirco R, Liu X W, Jung K K, Kim H R (2006). Novel functions of TIMPs in cell signaling. Cancer Metastasis Rev, 25, 99-113. https://doi.org/10.1007/s10555-006-7893-x
  9. Choudhuri T, Pal S, Das T, Sa G (2005). Curcumin selectively induces apoptosis in deregulated cyclin D1-expressed cells at G2 phase of cell cycle in a p53-dependent manner. J Biol Chem, 280, 20059-68. https://doi.org/10.1074/jbc.M410670200
  10. Curran S, Dundas S R, Buxton J, et al (2004). Matrix metalloproteinase/tissue inhibitors of matrix metalloproteinase phenotype identifies poor prognosis colorectal cancers. Clin Cancer Res, 10, 8229-34. https://doi.org/10.1158/1078-0432.CCR-04-0424
  11. Decock J, Hendrickx W, Drijkoningen M, et al (2007). Matrix metalloproteinase expression patterns in luminal A type breast carcinomas. Dis Markers, 23, 189-96. https://doi.org/10.1155/2007/281727
  12. Dorai T, Dutcher J P, Dempster D W, Wiernik P H (2004). Therapeutic potential of curcumin in prostate cancer--V: Interference with the osteomimetic properties of hormone refractory C4-2B prostate cancer cells. Prostate, 60, 1-17. https://doi.org/10.1002/pros.10359
  13. Figueira R C, Gomes L R, Neto J S, et al (2009). Correlation between MMPs and their inhibitors in breast cancer tumor tissue specimens and in cell lines with different metastatic potential. BMC Cancer, 9, 20. https://doi.org/10.1186/1471-2407-9-20
  14. Finan K M, Hodge G, Reynolds A M, et al (2006). In vitro susceptibility to the pro-apoptotic effects of TIMP-3 gene delivery translates to greater in vivo efficacy versus gene delivery for TIMPs-1 or -2. Lung Cancer, 53, 273-84. https://doi.org/10.1016/j.lungcan.2006.06.006
  15. Forget M A, Desrosiers R R, Beliveau R (1999). Physiological roles of matrix metalloproteinases: implications for tumor growth and metastasis. Can J Physiol Pharmacol, 77, 465-80. https://doi.org/10.1139/y99-055
  16. Gao W, Chan J Y, Wei W I, Wong T S (2012). Anti-Cancer Effects of Curcumin On Head And Neck Cancers. Anticancer Agents Med Chem.
  17. Huang M T, Lou Y R, Ma W, et al (1994). Inhibitory effects of dietary curcumin on forestomach, duodenal, and colon carcinogenesis in mice. Cancer Res, 54, 5841-7.
  18. Iwasaki M, Nishikawa A, Fujimoto T, et al (2002). Anti-invasive effect of MMI-166, a new selective matrix metalloproteinase inhibitor, in cervical carcinoma cell lines. Gynecol Oncol, 85, 103-7. https://doi.org/10.1006/gyno.2001.6573
  19. Jiang Y, Goldberg I D, Shi Y E (2002). Complex roles of tissue inhibitors of metalloproteinases in cancer. Oncogene, 21, 2245-52. https://doi.org/10.1038/sj.onc.1205291
  20. John A, Tuszynski G (2001). The role of matrix metalloproteinases in tumor angiogenesis and tumor metastasis. Pathol Oncol Res, 7, 14-23. https://doi.org/10.1007/BF03032599
  21. Kato Y, Yamashita T, Ishikawa M (2002). Relationship between expression of matrix metalloproteinase-2 and matrix metalloproteinase-9 and invasion ability of cervical cancer cells. Oncol Rep, 9, 565-9.
  22. Khokha R (1994). Suppression of the tumorigenic and metastatic abilities of murine B16-F10 melanoma cells in vivo by the overexpression of the tissue inhibitor of the metalloproteinases-1. J Natl Cancer Inst, 86, 299-304. https://doi.org/10.1093/jnci/86.4.299
  23. Kim H J, Park C I, Park B W, Lee H D, Jung W H (2006). Expression of MT-1 MMP, MMP2, MMP9 and TIMP2 mRNAs in ductal carcinoma in situ and invasive ductal carcinoma of the breast. Yonsei Med J, 47, 333-42. https://doi.org/10.3349/ymj.2006.47.3.333
  24. Kohrmann A, Kammerer U, Kapp M, Dietl J, Anacker J (2009). Expression of matrix metalloproteinases (MMPs) in primary human breast cancer and breast cancer cell lines: New findings and review of the literature. BMC Cancer, 9, 188. https://doi.org/10.1186/1471-2407-9-188
  25. Kotzsch M, Farthmann J, Meye A, et al (2005). Prognostic relevance of uPAR-del4/5 and TIMP-3 mRNA expression levels in breast cancer. Eur J Cancer, 41, 2760-8. https://doi.org/10.1016/j.ejca.2005.09.002
  26. Kunnumakkara A B, Anand P, Aggarwal B B (2008). Curcumin inhibits proliferation, invasion, angiogenesis and metastasis of different cancers through interaction with multiple cell signaling proteins. Cancer Lett, 269, 199-225. https://doi.org/10.1016/j.canlet.2008.03.009
  27. Lee C W, Lin W N, Lin C C, et al (2006). Transcriptional regulation of VCAM-1 expression by tumor necrosis factor-alpha in human tracheal smooth muscle cells: involvement of MAPKs, NF-kappaB, p300, and histone acetylation. J Cell Physiol, 207, 174-86. https://doi.org/10.1002/jcp.20549
  28. Li H C, Cao D C, Liu Y, et al (2004). Prognostic value of matrix metalloproteinases (MMP-2 and MMP-9) in patients with lymph node-negative breast carcinoma. Breast Cancer Res Treat, 88, 75-85. https://doi.org/10.1007/s10549-004-1200-8
  29. Lin L, Wang P, Zhao X L (2012). Study on curcumin-induced apoptosis in ovarian cancer resistant cell lines COC1/DDP. Sichuan Da Xue Xue Bao Yi Xue Ban, 43, 335-9 (in Chinese).
  30. Maheshwari R K, Singh A K, Gaddipati J, Srimal R C (2006). Multiple biological activities of curcumin: a short review. Life Sci, 78, 2081-7. https://doi.org/10.1016/j.lfs.2005.12.007
  31. Mannello F, Luchetti F, Falcieri E, Papa S (2005). Multiple roles of matrix metalloproteinases during apoptosis. Apoptosis, 10, 19-24. https://doi.org/10.1007/s10495-005-6058-7
  32. Martin D C, Ruther U, Sanchez-Sweatman O H, Orr F W, Khokha R (1996). Inhibition of SV40 T antigen-induced hepatocellular carcinoma in TIMP-1 transgenic mice. Oncogene, 13, 569-76.
  33. Montgomery A M, Mueller B M, Reisfeld R A, Taylor S M, DeClerck Y A (1994). Effect of tissue inhibitor of the matrix metalloproteinases-2 expression on the growth and spontaneous metastasis of a human melanoma cell line. Cancer Res, 54, 5467-73.
  34. Munshi H G, Wu Y I, Mukhopadhyay S, et al (2004). Differential regulation of membrane type 1-matrix metalloproteinase activity by ERK 1/2- and p38 MAPK-modulated tissue inhibitor of metalloproteinases 2 expression controls transforming growth factor-beta1-induced pericellular collagenolysis. J Biol Chem, 279, 39042-50. https://doi.org/10.1074/jbc.M404958200
  35. Mylona E, Magkou C, Giannopoulou I, et al (2006). Expression of tissue inhibitor of matrix metalloproteinases (TIMP)-3 protein in invasive breast carcinoma: relation to tumor phenotype and clinical outcome. Breast Cancer Res, 8, 57.
  36. Nagaraju G P, Aliya S, Zafar S F, et al (2012). The impact of curcumin on breast cancer. Integr Biol, (in press).
  37. Nagase H, Visse R, Murphy G (2006). Structure and function of matrix metalloproteinases and TIMPs. Cardiovasc Res, 69, 562-73. https://doi.org/10.1016/j.cardiores.2005.12.002
  38. Notoya M, Nishimura H, Woo J T, et al (2006). Curcumin inhibits the proliferation and mineralization of cultured osteoblasts. Eur J Pharmacol, 534, 55-62. https://doi.org/10.1016/j.ejphar.2006.01.028
  39. Overall C M, Lopez-Otin C (2002). Strategies for MMP inhibition in cancer: innovations for the post-trial era. Nat Rev Cancer, 2, 657-72. https://doi.org/10.1038/nrc884
  40. Pacheco M M, Mourao M, Mantovani E B, Nishimoto I N, Brentani M M (1998). Expression of gelatinases A and B, stromelysin-3 and matrilysin genes in breast carcinomas: clinico-pathological correlations. Clin Exp Metastasis, 16, 577-85. https://doi.org/10.1023/A:1006580415796
  41. Park J, Conteas C N. Anti-carcinogenic properties of curcumin on colorectal cancer. World J Gastrointest Oncol, 2, 169-76.
  42. Park M J, Kim E H, Park I C, et al (2002). Curcumin inhibits cell cycle progression of immortalized human umbilical vein endothelial (ECV304) cells by up-regulating cyclin-dependent kinase inhibitor, p21WAF1/CIP1, p27KIP1 and p53. Int J Oncol, 21, 379-83.
  43. Perkins S, Verschoyle R D, Hill K, et al (2002). Chemopreventive efficacy and pharmacokinetics of curcumin in the min/+ mouse, a model of familial adenomatous polyposis. Cancer Epidemiol Biomarkers Prev, 11, 535-40.
  44. Philip S, Bulbule A, Kundu G C (2004). Matrix metalloproteinase-2: mechanism and regulation of NF-kappaB-mediated activation and its role in cell motility and ECM-invasion. Glycoconj J, 21, 429-41. https://doi.org/10.1007/s10719-004-5533-7
  45. Przybylowska K, Kluczna A, Zadrozny M, et al (2006). Polymorphisms of the promoter regions of matrix metalloproteinases genes MMP-1 and MMP-9 in breast cancer. Breast Cancer Res Treat, 95, 65-72. https://doi.org/10.1007/s10549-005-9042-6
  46. Pulukuri S M, Patibandla S, Patel J, Estes N, Rao J S (2007). Epigenetic inactivation of the tissue inhibitor of metalloproteinase-2 (TIMP-2) gene in human prostate tumors. Oncogene, 26, 5229-37. https://doi.org/10.1038/sj.onc.1210329
  47. Qi JH, Ebrahem Q, Moore N, et al (2003). A novel function for tissue inhibitor of metalloproteinases-3 (TIMP3): inhibition of angiogenesis by blockage of VEGF binding to VEGF receptor-2. Nat Med, 9, 407-15. https://doi.org/10.1038/nm846
  48. Ranogajec I, Jakic-Razumovic J, Puzovic V, Gabrilovac J (2012). Prognostic value of matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9) and aminopeptidase N/CD13 in breast cancer patients. Med Oncol, 29, 561-9. https://doi.org/10.1007/s12032-011-9984-y
  49. Ree A H, Florenes V A, Berg J P, et al (1997). High levels of messenger RNAs for tissue inhibitors of metalloproteinases (TIMP-1 and TIMP-2) in primary breast carcinomas are associated with development of distant metastases. Clin Cancer Res, 3, 1623-8.
  50. Shishodia S, Chaturvedi M M, Aggarwal B B (2007). Role of curcumin in cancer therapy. Curr Probl Cancer, 31, 243-305. https://doi.org/10.1016/j.currproblcancer.2007.04.001
  51. Sintara K, Thong-Ngam D, Patumraj S, Klaikeaw N (2012). Curcumin attenuates gastric cancer induced by N-methyl-N-nitrosourea and saturated sodium chloride in rats. J Biomed Biotechnol, 915380.
  52. Stetler-Stevenson W G (2008). The tumor microenvironment: regulation by MMP-independent effects of tissue inhibitor of metalloproteinases-2. Cancer Metastasis Rev, 27, 57-66. https://doi.org/10.1007/s10555-007-9105-8
  53. Stetler-Stevenson W G, Seo D W (2005). TIMP-2: an endogenous inhibitor of angiogenesis. Trends Mol Med, 11, 97-103. https://doi.org/10.1016/j.molmed.2005.01.007
  54. Sun J (2010). Matrix Metalloproteinases and Tissue Inhibitor of Metalloproteinases Are Essential for the Inflammatory Response in Cancer Cells. J Signal Transuct.
  55. Valente P, Fassina G, Melchiori A, et al (1998). TIMP-2 over-expression reduces invasion and angiogenesis and protects B16F10 melanoma cells from apoptosis. Int J Cancer, 75, 246-53. https://doi.org/10.1002/(SICI)1097-0215(19980119)75:2<246::AID-IJC13>3.0.CO;2-B
  56. Vizoso F J, Gonzalez L O, Corte M D, et al (2007). Study of matrix metalloproteinases and their inhibitors in breast cancer. Br J Cancer, 96, 903-11. https://doi.org/10.1038/sj.bjc.6603666
  57. Woo M S, Jung S H, Kim S Y, et al (2005). Curcumin suppresses phorbol ester-induced matrix metalloproteinase-9 expression by inhibiting the PKC to MAPK signaling pathways in human astroglioma cells. Biochem Biophys Res Commun, 335, 1017-25. https://doi.org/10.1016/j.bbrc.2005.07.174
  58. Yang C L, Liu Y Y, Ma Y G, et al (2012). Curcumin Blocks Small Cell Lung Cancer Cells Migration, Invasion, Angiogenesis, Cell Cycle and Neoplasia through Janus Kinase-STAT3 Signalling Pathway. PLoS One, 7, 37960. https://doi.org/10.1371/journal.pone.0037960
  59. Zhang Y G, Du J, Tian X X, Zhong Y F, Fang W G (2007). Expression of E-cadherin, beta-catenin, cathepsin D, gelatinases and their inhibitors in invasive ductal breast carcinomas. Chin Med J, 120, 1597-605.
  60. Zheng S, Chen A (2004). Activation of PPARgamma is required for curcumin to induce apoptosis and to inhibit the expression of extracellular matrix genes in hepatic stellate cells in vitro. Biochem J, 384, 149-57. https://doi.org/10.1042/BJ20040928

Cited by

  1. Curcumin Inhibits TGF-β1-Induced MMP-9 and Invasion through ERK and Smad Signaling in Breast Cancer MDA-MB-231 Cells vol.13, pp.11, 2012, https://doi.org/10.7314/APJCP.2012.13.11.5709
  2. Effect of Botulinum Toxin A on Proliferation and Apoptosis in the T47D Breast Cancer Cell Line vol.14, pp.2, 2013, https://doi.org/10.7314/APJCP.2013.14.2.891
  3. Curcuma Contra Cancer? Curcumin and Hodgkin's Lymphoma vol.6, pp.1179-0644, 2013, https://doi.org/10.4137/CGM.S11113
  4. Hericium erinaceus (Lion’s Mane) Mushroom Extracts Inhibit Metastasis of Cancer Cells to the Lung in CT-26 Colon Cancer-Tansplanted Mice vol.61, pp.20, 2013, https://doi.org/10.1021/jf400916c
  5. Suppression of Human Breast Cancer Cell Metastasis by Coptisine in Vitro vol.15, pp.14, 2014, https://doi.org/10.7314/APJCP.2014.15.14.5747
  6. Cinobufacin Suppresses Cell Proliferation via miR-494 in BGC-823 Gastric Cancer Cells vol.15, pp.3, 2014, https://doi.org/10.7314/APJCP.2014.15.3.1241
  7. Curcumin and Inflammatory Bowel Disease: Potential and Limits of Innovative Treatments vol.19, pp.12, 2014, https://doi.org/10.3390/molecules191221127
  8. TIMP-3 -1296 T>C and TIMP-4 -55 T>C gene polymorphisms play a role in the susceptibility of hepatocellular carcinoma among women vol.35, pp.9, 2014, https://doi.org/10.1007/s13277-014-2170-z
  9. Small Activating RNA Restores the Activity of the Tumor Suppressor HIC-1 on Breast Cancer vol.9, pp.1, 2014, https://doi.org/10.1371/journal.pone.0086486
  10. Epigenetics in Gastric Carcinogenesis: Tet Genes as Important Players vol.36, pp.5, 2015, https://doi.org/10.1080/15321819.2015.1017402
  11. To study the effect of curcumin on the growth properties of circulating endothelial progenitor cells vol.51, pp.5, 2015, https://doi.org/10.1007/s11626-014-9852-0
  12. MiR125a-5p acting as a novel Gab2 suppressor inhibits invasion of glioma vol.55, pp.1, 2015, https://doi.org/10.1002/mc.22256
  13. Conjugation of curcumin-loaded lipid nanoemulsions with cell-penetrating peptides increases their cellular uptake and enhances the anti-inflammatory effects in endothelial cells vol.68, pp.2, 2016, https://doi.org/10.1111/jphp.12513
  14. Curcumin Inhibits Gastric Carcinoma Cell Growth and Induces Apoptosis by Suppressing the Wnt/β-Catenin Signaling Pathway vol.23, pp.1643-3750, 2017, https://doi.org/10.12659/MSM.902711
  15. Therapeutic potential of novel formulated forms of curcumin in the treatment of breast cancer by the targeting of cellular and physiological dysregulated pathways vol.233, pp.3, 2017, https://doi.org/10.1002/jcp.25961
  16. The Inhibitory Effect of C-phycocyanin Containing Protein Extract (C-PC Extract) on Human Matrix Metalloproteinases (MMP-2 and MMP-9) in Hepatocellular Cancer Cell Line (HepG2) vol.36, pp.3, 2017, https://doi.org/10.1007/s10930-017-9707-0
  17. Chemoprevention in gastrointestinal physiology and disease. Targeting the progression of cancer with natural products: a focus on gastrointestinal cancer vol.310, pp.9, 2016, https://doi.org/10.1152/ajpgi.00201.2015
  18. Curcumin prevents strokes in stroke-prone spontaneously hypertensive rats by improving vascular endothelial function vol.18, pp.1, 2018, https://doi.org/10.1186/s12872-018-0768-6
  19. In vitro and in vivo activity of liposome-encapsulated curcumin for naturally occurring canine cancers pp.14765810, 2018, https://doi.org/10.1111/vco.12424
  20. Mechanistic evaluation of phytochemicals in breast cancer remedy: current understanding and future perspectives vol.8, pp.52, 2018, https://doi.org/10.1039/C8RA04879G