Reports of Biochemistry
and Molecular Biology
Fri, Apr 4, 2025
[Archive]
Volume 13, Issue 2 (Vol.13 No.2 Jul 2024)
rbmb.net 2024, 13(2): 254-262 |
Back to browse issues page
Download citation:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:
Alaee M, Shahsavari G, Yazdi M, Hormozi M. 3,4 Dihydroxyphenylethanol May Inhibit Metastasis in HepG2 Cells by Influencing the Expression of miR-21 and Genes Associated with Metastasis. rbmb.net 2024; 13 (2) :254-262
URL: http://rbmb.net/article-1-1370-en.html
URL: http://rbmb.net/article-1-1370-en.html
Razi Herbal Medicines Research Center, School of Medicine, Lorestan University of Medical Sciences, Khorramabad, Iran.
Abstract: (546 Views)
Background: Hepatocellular carcinoma (HCC) is one of the lethal malignancies with a poor prognosis due to metastatic complications. Matrix metalloproteinases (MMPs) and their inhibitors, tissue inhibitors of metalloproteinases (TIMPs), have an important role in metastasis. MicroRNA-21 (miR-21) is significantly overexpressed in nearly all types of human cancers, including HCC. Targeting miR-21 pharmacologically could be a promising therapeutic approach for HCC. 3,4-dihydroxyphenylethanol (DHPE), a phenolic phytochemical compound found in olive, has potent antioxidant and anticancer properties. This study aimed to investigate the effect of DHPE on the expression of miR-21 with genes associated with metastasis (MMP-2, MMP-9, TIMP-1, and TIMP-2) and their correlation with miR-21 in HepG2 cells.
Methods: This experimental study had four groups, including a control, and three groups of treatment with different concentrations of DHPE (50, 100, and 150 µM) for 24 hours. The expression levels of genes were determined by RT-qPCR.
Results: The results showed that the treatment of cells with DHPE significantly reduced the expression of miR-21, MMP-2, MMP-9, and TIMP-1 but increased TIMP-2 compared to the control group; additionally, there was a negative correlation between miR-21 and TIMP-2 but a positive correlation between miR-21 with MMP-2, MMP-9, and TIMP-1.
Conclusion: The results showed that DHPE, likely by reducing the expression of miR-21, can increase TIMP-2 and reduce MMP-2, MMP-9, and TIMP-1 gene expression and may play a role in inhibiting cell migration in HepG2 cells.
Methods: This experimental study had four groups, including a control, and three groups of treatment with different concentrations of DHPE (50, 100, and 150 µM) for 24 hours. The expression levels of genes were determined by RT-qPCR.
Results: The results showed that the treatment of cells with DHPE significantly reduced the expression of miR-21, MMP-2, MMP-9, and TIMP-1 but increased TIMP-2 compared to the control group; additionally, there was a negative correlation between miR-21 and TIMP-2 but a positive correlation between miR-21 with MMP-2, MMP-9, and TIMP-1.
Conclusion: The results showed that DHPE, likely by reducing the expression of miR-21, can increase TIMP-2 and reduce MMP-2, MMP-9, and TIMP-1 gene expression and may play a role in inhibiting cell migration in HepG2 cells.
Keywords: HepG2 cells, miR-21, Matrix Metalloproteinases, Tissue Inhibitor of Metalloproteinases, 3, 4-Dihydroxyphenylethanol.
Type of Article: Original Article |
Subject:
Molecular Biology
Received: 2024/04/11 | Accepted: 2024/08/19 | Published: 2025/01/4
Received: 2024/04/11 | Accepted: 2024/08/19 | Published: 2025/01/4
References
1. Lin YL, Li Y. Study on the hepatocellular carcinoma model with metastasis. Genes Dis. 2020;7(3): 336-350. [DOI:10.1016/j.gendis.2019.12.008] [PMID] []
2. Sun Y, Ma L. The emerging molecular machinery and therapeutic targets of metastasis. Trends Pharmacol Sci. 2015;36(6):349-59. [DOI:10.1016/j.tips.2015.04.001] [PMID] []
3. Winer A, Adams S, Mignatti P. Matrix Metalloproteinase Inhibitors in Cancer Therapy: Turning Past Failures into Future Successes. Molecular Cancer Therapeutics. 2018;17(6):1147-1155. [DOI:10.1158/1535-7163.MCT-17-0646] [PMID] []
4. Zhou W, Yu X, Sun S, Zhang X, Yang W, Zhang J, et al. Increased expression of MMP-2 and MMP-9 indicates poor prognosis in glioma recurrence. Biomed Pharmacother. 2019;118:109369. [DOI:10.1016/j.biopha.2019.109369] [PMID]
5. Ochoa-Callejero L, Toshkov I, Menne S, Martínez A. Expression of matrix metalloproteinases and their inhibitors in the woodchuck model of hepatocellular carcinoma. J Med Virol. 2013;85(7):1127-38. [DOI:10.1002/jmv.23571] [PMID]
6. Rohan TE, Wang T, Weinmann S, Wang Y, Lin J, Ginsberg M, Loudig O. A miRNA Expression Signature in Breast Tumor Tissue Is Associated with Risk of Distant Metastasis. Cancer Res. 2019;79(7):1705-1713. [DOI:10.1158/0008-5472.CAN-18-2779] [PMID]
7. Wang J, Chu Y, Xu M, Zhang X, Zhou Y, Xu M. miR-21 promotes cell migration and invasion of hepatocellular carcinoma by targeting KLF5. Oncol Lett. 2019;17(2):2221-2227. [DOI:10.3892/ol.2018.9843]
8. Nooh M, Hakemi-Vala M, Nowroozi J, Fatemi SR, Dezfulian M. Prediction of Blood miRNA-mRNA Regulatory Network in Gastric Cancer. Rep Biochem Mol Biol. 2021;10(2):243-256. [DOI:10.52547/rbmb.10.2.243] [PMID] []
9. Robles-Almazan M, Pulido-Moran M, Moreno-Fernandez J, Ramirez-Tortosa C, Rodriguez-Garcia C, Quiles JL, Ramirez-Tortosa M. Hydroxytyrosol: Bioavailability, toxicity, and clinical applications. Food Res Int. 2018;105:654-667. [DOI:10.1016/j.foodres.2017.11.053] [PMID]
10. Imran M, Nadeem M, Gilani SA, Khan S, Sajid MW, Amir RM. Antitumor Perspectives of Oleuropein and Its Metabolite Hydroxytyrosol: Recent Updates. J Food Sci. 2018;83(7):1781-1791. [DOI:10.1111/1750-3841.14198] [PMID]
11. Cruz-Lozano M, González-González A, Marchal JA, Muñoz-Muela E, Molina MP, Cara FE, et al. Hydroxytyrosol inhibits cancer stem cells and the metastatic capacity of triple-negative breast cancer cell lines by the simultaneous targeting of epithelial-to-mesenchymal transition, Wnt/β-catenin and TGFβ signaling pathways. Eur J Nutr. 2019;58(8):3207-3219. [DOI:10.1007/s00394-018-1864-1] [PMID]
12. Lu HY, Zhu JS, Zhang Z, Shen WJ, Jiang S, Long YF, et al. Hydroxytyrosol and Oleuropein Inhibit Migration and Invasion of MDA-MB-231 Triple-Negative Breast Cancer Cell via Induction of Autophagy. Anticancer Agents Med Chem. 2019;19(16):1983-1990. [DOI:10.2174/1871520619666190722101207] [PMID]
13. Pfaffl MW, Horgan GW, Dempfle L. Relative expression software tool (REST) for group-wise comparison and statistical analysis of relative expression results in real-time PCR. Nucleic Acids Res. 2002;30(9):e36. [DOI:10.1093/nar/30.9.e36] [PMID] []
14. Wang W, Li D, Xiang L, Lv M, Tao L, Ni T, et al. TIMP-2 inhibits metastasis and predicts prognosis of colorectal cancer via regulating MMP-9. Cell Adh Migr. 2019;13(1):273-284. [DOI:10.1080/19336918.2019.1639303] [PMID] []
15. León-González AJ, Sáez-Martínez P, Jiménez-Vacas JM, Herrero-Aguayo V, Montero-Hidalgo AJ, Gómez-Gómez E, et al. Comparative Cytotoxic Activity of Hydroxytyrosol and Its Semisynthetic Lipophilic Derivatives in Prostate Cancer Cells. Antioxidants (Basel). 2021;10(9):1348. [DOI:10.3390/antiox10091348] [PMID] []
16. Ramirez-Tortosa C, Sanchez A, Perez-Ramirez C, Quiles JL, Robles-Almazan M, Pulido-Moran M, et al. Hydroxytyrosol Supplementation Modifies Plasma Levels of Tissue Inhibitor of Metallopeptidase 1 in Women with Breast Cancer. Antioxidants (Basel). 2019;8(9):393. [DOI:10.3390/antiox8090393] [PMID] []
17. Lu HY, Zhu JS, Xie J, Zhang Z, Zhu J, Jiang S, et al. Hydroxytyrosol and Oleuropein Inhibit Migration and Invasion via Induction of Autophagy in ER-Positive Breast Cancer Cell Lines (MCF7 and T47D). Nutr Cancer. 2021;73(2):350-360. [DOI:10.1080/01635581.2020.1750661] [PMID]
18. Bautista-Sánchez D, Arriaga-Canon C, Pedroza-Torres A, De La Rosa-Velázquez IA, González-Barrios R, Contreras-Espinosa L, et al. The Promising Role of miR-21 as a Cancer Biomarker and Its Importance in RNA-Based Therapeutics. Mol Ther Nucleic Acids. 2020;20:409-420. [DOI:10.1016/j.omtn.2020.03.003] [PMID] []
19. Kamil Alhassbalawi N, Zare Ebrahimabad M, Seyedhosseini FS, Bagheri Y, Abdollahi N, Nazari A, et al. Circulating miR-21 Overexpression Correlates with PDCD4 and IL-10 in Systemic Lupus Erythematosus (SLE): A Promising Diagnostic and Prognostic Biomarker. Rep Biochem Mol Biol. 2023;12(2):220-232. [DOI:10.61186/rbmb.12.2.220] [PMID] []
20. Fan B, Jin Y, Zhang H, Zhao R, Sun M, Sun M, et al. MicroRNA 21 contributes to renal cell carcinoma cell invasiveness and angiogenesis via the PDCD4/c Jun (AP 1) signalling pathway. Int J Oncol. 2020;56(1):178-192. [DOI:10.3892/ijo.2019.4928]
21. Abtin M, Alivand MR, Khaniani MS, Bastami M, Zaeifizadeh M, Derakhshan SM. Simultaneous downregulation of miR-21 and miR-155 through oleuropein for breast cancer prevention and therapy. J Cell Biochem. 2018;119(9):7151-7165. [DOI:10.1002/jcb.26754] [PMID]
22. Gui F, Hong Z, You Z, Wu H, Zhang Y. MiR-21 inhibitor suppressed the progression of retinoblastoma via the modulation of PTEN/PI3K/AKT pathway. Cell Biol Int. 2016;40(12):1294-1302. [DOI:10.1002/cbin.10678] [PMID]
23. Coccia A, Bastianelli D, Mosca L, Monticolo R, Panuccio I, Carbone A, et al. Extra virgin olive oil phenols suppress migration and invasion of T24 human bladder cancer cells through modulation of matrix metalloproteinase-2. Nutr Cancer. 2014;66(6):946-54. [DOI:10.1080/01635581.2014.922204] [PMID]
24. Scoditti E, Calabriso N, Massaro M, Pellegrino M, Storelli C, Martines G, et al. Mediterranean diet polyphenols reduce inflammatory angiogenesis through MMP-9 and COX-2 inhibition in human vascular endothelial cells: a potentially protective mechanism in atherosclerotic vascular disease and cancer. Arch Biochem Biophys. 2012;527(2):81-9. [DOI:10.1016/j.abb.2012.05.003] [PMID]
25. Carpén T, Sorsa T, Jouhi L, Tervahartiala T, Haglund C, Syrjänen S, et al. High levels of tissue inhibitor of metalloproteinase-1 (TIMP-1) in the serum are associated with poor prognosis in HPV-negative squamous cell oropharyngeal cancer. Cancer Immunol Immunother. 2019;68(8):1263-1272. [DOI:10.1007/s00262-019-02362-4] [PMID] []
26. García-Vilas JA, Quesada AR, Medina MÁ. Hydroxytyrosol targets extracellular matrix remodeling by endothelial cells and inhibits both ex vivo and in vivo angiogenesis. Food Chem. 2017;221:1741-1746. [DOI:10.1016/j.foodchem.2016.10.111] [PMID]
27. Peeney D, Jensen SM, Castro NP, Kumar S, Noonan S, Handler C, et al. TIMP-2 suppresses tumor growth and metastasis in murine model of triple-negative breast cancer. Carcinogenesis. 2020;41(3):313-325. [DOI:10.1093/carcin/bgz172] [PMID] []
28. Escalona RM, Bilandzic M, Western P, Kadife E, Kannourakis G, Findlay JK, Ahmed N. TIMP-2 regulates proliferation, invasion and STAT3-mediated cancer stem cell-dependent chemoresistance in ovarian cancer cells. BMC Cancer. 2020;20(1):960. [DOI:10.1186/s12885-020-07274-6] [PMID] []
29. Gervasi F, Pojero F. Use of Oleuropein and Hydroxytyrosol for Cancer Prevention and Treatment: Considerations about How Bioavailability and Metabolism Impact Their Adoption in Clinical Routine. Biomedicines. 2024;12(3):502. [DOI:10.3390/biomedicines12030502] [PMID] []
30. Bertelli M, Kiani AK, Paolacci S, Manara E, Kurti D, Dhuli K, et al. Hydroxytyrosol: A natural compound with promising pharmacological activities. J Biotechnol. 2020;309:29-33. [DOI:10.1016/j.jbiotec.2019.12.016] [PMID]
Send email to the article author
| Rights and permissions | |
 |
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
