Volume 13, Issue 3 (Vol.13 No.3 Oct 2024)                   rbmb.net 2024, 13(3): 329-340 | Back to browse issues page


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Farzaneh S, Salehypour M, Tafvizi F, Naseh V. The Effect of Curcumin on the Activity of MMP-17 and MMP-24 in Hepatocytes of Mice Exposed to Thioacetamide. rbmb.net 2024; 13 (3) :329-340
URL: http://rbmb.net/article-1-1408-en.html
Department of Biology, Islamic Azad university of Parand Branch, Parand, Iran.
Abstract:   (554 Views)
Background: Hepatocellular carcinoma is the most primitive form of liver cancer, which is related to chemo carcinogens such as thioacetamide (TAA) and tissue remodeling molecules such as Matrix metalloproteinases (MMPs). Antioxidants, like curcumin (Cur), can inhibit these factors. In this research, the effect of curcumin on the expression and activity of two MMP enzymes, MMP-14 and MMP-17, which are involved in the carcinogenesis of mice after chronic exposure to thioacetamide, is investigated.

Methods: In this study, 30 mice were divided into six groups and studied for 4 months. The first group, control; the second group, curcumin; the third group, TAA; the fourth group, TAA and curcumin simultaneously; the fifth group, first treated with TAA for 2 months and then curcumin; and finally, the sixth group, first treated with curcumin for 2 months and then TAA. Afterward, the mice were euthanized, and their liver tissues were transferred to the laboratory for analysis of gene and protein expression.

Results: The averages of gene expression were calculated using SigmaPlot software and showed that the expression of MMP-17 and MMP-24 genes and the levels of their proteins were significantly increased by thioacetamide (****p< 0001) compared to the control group. Pathological observations indicated necrosis and dysplastic foci in the TAA group.

Conclusion: Considering the crucial roles of MMPs in various diseases, including hepatocellular carcinoma, the regulation of their gene expression and enzymatic activity is significant in preventing tumor progression. Compounds such as thioacetamide and polyphenols like curcumin can modulate the activity of MMP-17 and MMP-24.

Full-Text [PDF 1538 kb]   (154 Downloads)    
Type of Article: Original Article | Subject: Molecular Biology
Received: 2024/06/5 | Accepted: 2025/01/9 | Published: 2025/04/12

References
1. King RJB. Cancer Biology, 2nd edn. Prentice Hall, Edinburgh. 2000.
2. Chen C, Wang G. Mechanisms of hepatocellular carcinoma and challenges and opportunities for molecular targeted therapy. World J Hepatol. 2015;7(15):1964-70. [DOI:10.4254/wjh.v7.i15.1964] [PMID] []
3. Cui N, Hu M, Khalil RA. Biochemical and Biological Attributes of Matrix Metalloproteinases. Prog Mol Biol Transl Sci. 2017;147:1-73. [DOI:10.1016/bs.pmbts.2017.02.005] [PMID] []
4. Hua H, Li M, Luo T, Yin Y, Jiang Y. Matrix metalloproteinases in tumorigenesis: an evolving paradigm. Cell Mol Life Sci. 2011;68(23):3853-68. [DOI:10.1007/s00018-011-0763-x] [PMID] []
5. Johansson N, Ahonen M, Kähäri VM. Matrix metalloproteinases in tumor invasion. Cell Mol Life Sci. 2000;57(1):5-15. [DOI:10.1007/s000180050495] [PMID] []
6. Pei D. Identification and characterization of the fifth membrane-type matrix metalloproteinase MT5-MMP. J Biol Chem. 1999 Mar 26;274(13):8925-32. [DOI:10.1074/jbc.274.13.8925] [PMID]
7. Itoh Y, Kajita M, Kinoh H, Mori H, Okada A, Seiki M. Membrane type 4 matrix metalloproteinase (MT4-MMP, MMP-17) is a glycosylphosphatidylinositol-anchored proteinase. J Biol Chem. 1999;274(48):34260-6. [DOI:10.1074/jbc.274.48.34260] [PMID]
8. Yip C, Foidart P, Noël A, Sounni NE. MT4-MMP: The GPI-Anchored Membrane-Type Matrix Metalloprotease with Multiple Functions in Diseases. Int J Mol Sci. 2019;20(2):354. [DOI:10.3390/ijms20020354] [PMID] []
9. Llano E, Pendás AM, Freije JP, Nakano A, Knäuper V, Murphy G, López-Otin C. Identification and characterization of human MT5-MMP, a new membrane-bound activator of progelatinase a overexpressed in brain tumors. Cancer Res. 1999;59(11):2570-6.
10. Santos NP, Colaço AA, Oliveira PA. Animal models as a tool in hepatocellular carcinoma research: A Review. Tumour Biol. 2017;39(3):1010428317695923. [DOI:10.1177/1010428317695923] [PMID]
11. Leenders MW, Nijkamp MW, Borel Rinkes IH. Mouse models in liver cancer research: a review of current literature. World J Gastroenterol. 2008;14(45):6915-23. [DOI:10.3748/wjg.14.6915] [PMID] []
12. Wogan GN. Impacts of chemicals on liver cancer risk. Semin Cancer Biol. 2000;10(3):201-10. [DOI:10.1006/scbi.2000.0320] [PMID]
13. Williams GM. Chemicals with carcinogenic activity in the rodent liver; mechanistic evaluation of human risk. Cancer Lett. 1997;117(2):175-88. [DOI:10.1016/S0304-3835(97)00229-2] [PMID]
14. Lee SJ, Yum YN, Kim SC, Kim Y, Lim J, Lee WJ, et al. Distinguishing between genotoxic and non-genotoxic hepatocarcinogens by gene expression profiling and bioinformatic pathway analysis. Sci Rep. 2013;3:2783. [DOI:10.1038/srep02783] [PMID] []
15. Zhang HE, Henderson JM, Gorrell MD. Animal models for hepatocellular carcinoma. Biochim Biophys Acta Mol Basis Dis. 2019;1865(5):993-1002. [DOI:10.1016/j.bbadis.2018.08.009] [PMID]
16. Sharma RA, Gescher AJ, Steward WP. Curcumin: the story so far. Eur J Cancer. 2005;41(13):1955-68. [DOI:10.1016/j.ejca.2005.05.009] [PMID]
17. Campbell FC, Collett GP. Chemopreventive properties of curcumin. Future Oncol. 2005;1(3):405-14. [DOI:10.1517/14796694.1.3.405] [PMID]
18. Cao F, Liu T, Xu Y, Xu D, Feng S. Curcumin inhibits cell proliferation and promotes apoptosis in human osteoclastoma cell through MMP-9, NF-κB and JNK signaling pathways. Int J Clin Exp Pathol. 2015;8(6):6037-45.
19. Okimoto RA, Breitenbuecher F, Olivas VR, Wu W, Gini B, Hofree M, et al. Inactivation of Capicua drives cancer metastasis. Nat Genet. 2017;49(1):87-96. [DOI:10.1038/ng.3728] [PMID] []
20. Chabottaux V, Sounni NE, Pennington CJ, English WR, van den Brûle F, Blacher S, et al. Membrane-type 4 matrix metalloproteinase promotes breast cancer growth and metastases. Cancer Res. 2006 66(10):5165-72. [DOI:10.1158/0008-5472.CAN-05-3012] [PMID]
21. English WR, Puente XS, Freije JM, Knauper V, Amour A, Merryweather A, et al. Membrane type 4 matrix metalloproteinase (MMP17) has tumor necrosis factor-alpha convertase activity but does not activate pro-MMP2. J Biol Chem. 2000;275(19):14046-55. [DOI:10.1074/jbc.275.19.14046] [PMID]
22. Ricci S, D'Esposito V, Oriente F, Formisano P, Di Carlo A. Substrate-zymography: a still worthwhile method for gelatinases analysis in biological samples. Clin Chem Lab Med. 2016;54(8):1281-90.
23. Nguyen-Lefebvre AT, Ajith A, Portik-Dobos V, Horuzsko DD, Arbab AS, Dzutsev A, et al. The innate immune receptor TREM-1 promotes liver injury and fibrosis. J Clin Invest. 2018;128(11):4870-4883. [DOI:10.1172/JCI98156] [PMID] []
24. Abdelhamid AM, Selim A, Zaafan MA. The Hepatoprotective Effect of Piperine Against Thioacetamide-Induced Liver Fibrosis in Mice: The Involvement of miR-17 and TGF-β/Smads Pathways. Front Mol Biosci. 2021;8:754098. [DOI:10.3389/fmolb.2021.754098] [PMID] []
25. Wallace MC, Hamesch K, Lunova M, Kim Y, Weiskirchen R, Strnad P, Friedman SL. Standard operating procedures in experimental liver research: thioacetamide model in mice and rats. Lab Anim. 2015;49(1 Suppl):21-9. [DOI:10.1177/0023677215573040] [PMID]
26. Towbin H, Staehelin T, Gordon J. Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci USA. 1979;76(9):4350-4. [DOI:10.1073/pnas.76.9.4350] [PMID] []
27. Lee TY, Chang HH, Wen CK, Huang TH, Chang YS. Modulation of thioacetamide-induced hepatic inflammations, angiogenesis and fibrosis by andrographolide in mice. J Ethnopharmacol. 2014;158 Pt A:423-30. [DOI:10.1016/j.jep.2014.10.056] [PMID]
28. Meis J, Khanna A. RNA amplification and cDNA synthesis for qRT-PCR directly from a single cell. Nat Methods. 2009; 6, i-ii. [DOI:10.1038/nmeth.f.261]
29. Yu J, He Z, He X, Luo Z, Lian L, Wu B, et al. Comprehensive Analysis of the Expression and Prognosis for MMPs in Human Colorectal Cancer. Front Oncol. 2021;11:771099. [DOI:10.3389/fonc.2021.771099] [PMID] []
30. Shishodia S. Molecular mechanisms of curcumin action: gene expression. Biofactors. 2013;39(1):37-55. [DOI:10.1002/biof.1041] [PMID]
31. Mahmoudi A, Butler AE, Majeed M, Banach M, Sahebkar A. Investigation of the Effect of Curcumin on Protein Targets in NAFLD Using Bioinformatic Analysis. Nutrients. 2022;14(7):1331. [DOI:10.3390/nu14071331] [PMID] []
32. Cao F, Liu T, Xu Y, Xu D, Feng S. Curcumin inhibits cell proliferation and promotes apoptosis in human osteoclastoma cell through MMP-9, NF-κB and JNK signaling pathways. Int J Clin Exp Pathol. 2015;8(6):6037-45.
33. Choi H, Chun YS, Shin YJ, Ye SK, Kim MS, Park JW. Curcumin attenuates cytochrome P450 induction in response to 2,3,7,8-tetrachlorodibenzo-p-dioxin by ROS-dependently degrading AhR and ARNT. Cancer Sci. 2008;99(12):2518-24. [DOI:10.1111/j.1349-7006.2008.00984.x] [PMID] []
34. Piper JT, Singhal SS, Salameh MS, Torman RT, Awasthi YC, Awasthi S. Mechanisms of anticarcinogenic properties of curcumin: the effect of curcumin on glutathione linked detoxification enzymes in rat liver. Int J Biochem Cell Biol. 1998;30(4):445-56. [DOI:10.1016/S1357-2725(98)00015-6] [PMID]
35. Mudduluru G, George-William JN, Muppala S, Asangani IA, Kumarswamy R, Nelson LD, Allgayer H. Curcumin regulates miR-21 expression and inhibits invasion and metastasis in colorectal cancer. Biosci Rep. 2011;31(3):185-97. [DOI:10.1042/BSR20100065] [PMID]
36. Killian PH, Kronski E, Michalik KM, Barbieri O, Astigiano S, Sommerhoff CP, et al. Curcumin inhibits prostate cancer metastasis in vivo by targeting the inflammatory cytokines CXCL1 and -2. Carcinogenesis. 2012;33(12):2507-19. [DOI:10.1093/carcin/bgs312] [PMID]
37. Zhang L, Cheng X, Gao Y, Zhang C, Bao J, Guan H, et al. Curcumin inhibits metastasis in human papillary thyroid carcinoma BCPAP cells via down-regulation of the TGF-β/Smad2/3 signaling pathway. Exp Cell Res. 2016;341(2):157-65. [DOI:10.1016/j.yexcr.2016.01.006] [PMID]
38. Wang ME, Chen YC, Chen IS, Hsieh SC, Chen SS, Chiu CH. Curcumin protects against thioacetamide-induced hepatic fibrosis by attenuating the inflammatory response and inducing apoptosis of damaged hepatocytes. J Nutr Biochem. 2012;23(10):1352-66. [DOI:10.1016/j.jnutbio.2011.08.004] [PMID]
39. García-Niño WR, Pedraza-Chaverrí J. Protective effect of curcumin against heavy metals-induced liver damage. Food Chem Toxicol. 2014;69:182-201. [DOI:10.1016/j.fct.2014.04.016] [PMID]
40. Chabottaux V, Sounni NE, Pennington CJ, English WR, van den Brûle F, Blacher S, et al. Membrane-type 4 matrix metalloproteinase promotes breast cancer growth and metastases. Cancer Res. 2006;66(10):5165-72. [DOI:10.1158/0008-5472.CAN-05-3012] [PMID]
41. Nuttall RK, Pennington CJ, Taplin J, Wheal A, Yong VW, Forsyth PA, Edwards DR. Elevated membrane-type matrix metalloproteinases in gliomas revealed by profiling proteases and inhibitors in human cancer cells. Mol Cancer Res. 2003;1(5):333-45.
42. Wang Y, Yu S, Li Y, Luo H. Expression and clinical significance of matrix metalloproteinase-17 and -25 in gastric cancer. Oncol Lett. 2015;9: 671-676. [DOI:10.3892/ol.2014.2747] [PMID] []
43. Sounni NE, Paye A, Host L, Noël A. MT-MMPS as Regulators of Vessel Stability Associated with Angiogenesis. Front Pharmacol. 2011;2:111. [DOI:10.3389/fphar.2011.00111] [PMID] []
44. Okimoto RA, Breitenbuecher F, Olivas VR, Wu W, Gini B, Hofree M, et al. Inactivation of Capicua drives cancer metastasis. Nat Genet. 2017;49(1):87-96. [DOI:10.1038/ng.3728] [PMID] []
45. Benson CS, Babu SD, Radhakrishna S, Selvamurugan N, Ravi Sankar B. Expression of matrix metalloproteinases in human breast cancer tissues. Dis Markers. 2013;34(6):395-405. [DOI:10.1155/2013/420914] [PMID] []

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