Middle East Journal of Cancer

Current Issue

By Issue

By Author

By Subject

Author Index

Keyword Index

About Journal

Aims and Scope

Editorial Board

Publication Ethics

Indexing and Abstracting

Related Links

FAQ

Peer Review Process

News

Forms

Journal Metrics

Comparison Anticancer Effects of Platinum Ribavirin with Platinum Azidothymidine via Telomerase, Bcl-2, miRNA-21 and miRNA-122 Biomarkers Genes Expression on HepG2 Cancer Cell Lines

Articles in Press

Document Type : Original Article(s)

Authors

1 Department of Biochemistry, Faculty of Medicine, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran

2 Department of Biochemistry and Biophysics, Faculty of Advanced Sciences and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran

3 Department of Biochemistry, Pasteur institute, Tehran, Iran

4 Blood Transfusion Research center, High institute for Research and Education in Transfusion Medicine, Tehran, Iran

10.30476/mejc.2025.104451.2183

Abstract

Background: Anticancer medication assessment is performed by numerous approaches including biomarkers gene expression. This study aimed to investigate the anticancer effects of Pt-Rb and Pt-AZTon HepG2 cells. 
Method: In this case-control study, four groups of cells were examined. Group A was the control group, group B was untreated cancer cells, and Groups C and D were treated with Pt-AZT and Pt-Rb, respectively. Using the MTT test, LC50 was determined, and the relative gene expression of the biomarkers was assessed by RNA extraction, cDNA synthesis and RT-PCR. Through histopathlogical study apoptotic regions of cells were compared. Data analysis was done using ANOVA and Turkey’s post hoc test.
Results: The results showed a significant increase for the proapoptotic gene miRNA-122 (19.97 ± 0 .04) in group D compared with group C (10.36 ± 0.007). Also, there was a significant decrease in the antiapoptotic genes in group D, including miRNA-21 (0.10 ± 0.014), telomerase (0.56 ± 0.480), and Bcl-2 (0.41 ± 0.276), compared with group C (miRNA-21: 2.0 ± 0.145, telomerase: 2.49 ± 0.231, and Bcl-2: 2.93 ± 0.276). There were significant differences between the nearly all studied groups (P < 0.05). There were more extensive apoptotic regions in group D compared with group C.
Conclusion: Using Pt-Rb has more benefits in terms of stronger anticancer effects than Pt-AZT on cancer cells. Also, lower drug resistance and lower side effects in Pt-Rb were considered compared with Pt-AZT, indicating that it can be more effective in anti-cancer therapy.

Highlights

Abdolreza Sabokrouh (Google Scholar)

Keywords

Main Subjects

This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination, and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.30476/mejc.2025.104451.2183

References
  1. Zaimy MA, Saffarzadeh N, Mohammadi A, Pourghadamyari H, Izadi P, Sarli A, et al. New methods in the diagnosis of cancer and gene therapy of cancer based on nanoparticles. Cancer Gene Ther. 2017;24(6):233-43. doi: 10.1038/cgt.2017.16.
  2. Kontomanolis EN, Koutras A, Syllaios A, Schizas D, Mastoraki A, Garmpis N, et al. Role of oncogenes and tumor-suppressor genes in carcinogenesis: A review. Anticancer Res. 2020;40(11):6009-15. doi: 10.21873/anticanres.14622.
  3. Wang LH, Wu CF, Rajasekaran N, Shin YK. Loss of tumor suppressor gene function in human cancer: An overview. Cell Physiol Biochem. 2018;51(6):2647-93. doi: 10.1159/000495956. PMID: 30562755.
  4. Sarhadi VK, Armengol G. Molecular biomarkers in cancer. 2022;12(8):1021. doi: 10.3390/biom12081021. PMID: 35892331; PMCID: PMC9331210.
  5. Smith EM, Pendlebury DF, Nandakumar J. Structural biology of telomeres and telomerase. Cell Mol Life Sci. 2020;77(1):61-79. doi: 10.1007/s00018-019-03369-x.
  6. Guterres AN, Villanueva J. Targeting telomerase for cancer therapy. 2020;39(36):5811-24. doi: 10.1038/s41388-020-01405-w.
  7. Jianyu F, Yushan Z, Quan C, Jialing L. Physiological Function and Structural Basis of Bcl-2 Family. [Article in Chinese] 2019;41(8):1477-89. PMID: 34249113; PMCID: PMC8265309.
  8. Lu TX, Rothenberg ME. MicroRNA. J Allergy Clin Immunol. 2018;141(4):1202-7. doi: 10.1016/j.jaci.2017.08.034. PMID: 29074454; PMCID: PMC5889965.
  9. Ratti M, Lampis A, Ghidini M, Salati M, Mirchev MB, Valeri N, et al. MicroRNAs (miRNAs) and long non-coding RNAs (lncRNAs) as new tools for cancer therapy: First steps from bench to bedside. Target Oncol. 2020;15(3):261-78. doi: 10.1007/s11523-020-00717-x.
  10. Ratnasari N, Lestari P, Renovaldi D, Raditya Ningsih J, Qoriansas N, Wardana T, et al. Potential plasma biomarkers: miRNA-29c, miRNA-21, and miRNA-155 in clinical progression of hepatocellular carcinoma patients. PLoS One. 2022;17(2):e0263298. doi: 10.1371/journal.pone.0263298. PMID: 35157721; PMCID: PMC8843218.
  11. Ghosh S. Cisplatin: The first metal based anticancer drug. Bioorg Chem. 2019;88:102925. doi: 10.1016/j.bioorg.2019.102925. PMID: 31003078.
  12. Sabokrouh A, Hajivand S, Atabi F. Comparison of anti-cancer effects of platinum ribavirin and ribavirin via telomerase and Bcl-2 gene expression. Naunyn Schmiedebergs Arch Pharmacol. 2024;397(6):3907-15. doi: 10.1007/s00210-023-02841-7.
  13. Sabokrouh A, Atabi F, Jassem RM, Mohammadi R. The anticancer efficacy of platinum azidothymidin on hepatocellular carcinoma via affecting the telomerase and the BcL-2 genes expression. J Gastrointest Cancer. 2020;51(3):813-7. doi: 10.1007/s12029-019-00296-9. PMID: 31471759.
  14. Sabokrouh A, Sadeghi Motlagh B, Atabi F. Study of anticancer effects of platinum levetiracetam and levetiracetam via cancer biomarkers genes expression on HepG2 cell line. Mol Biol Rep. 2023; 50(11):9431-9. doi: 10.1007/s11033-023-08890-8. PMID: 37831345.
  15. Mars JC, Ghram M, Culjkovic-Kraljacic B, Borden KLB. The cap-binding complex CBC and the eukaryotic translation factor eIF4E: Co-conspirators in cap-dependent RNA maturation and translation. Cancers (Basel). 2021;13(24):6185. doi: 10.3390/cancers13246185. PMID: 34944805; PMCID: PMC8699206.
  16. Karaki S, Andrieu C, Ziouziou H, Rocchi P. The eukaryotic translation initiation factor 4E (eIF4E) as a therapeutic target for cancer. Adv Protein Chem Struct Biol. 2015;101:1-26. doi: 10.1016/bs.apcsb.2015.09.001. PMID: 26572974; PMCID: PMC7185574.
  17. He L, Li H, Wu A, Peng Y, Shu G, Yin G. Functions of N6-methyladenosine and its role in cancer. Mol Cancer. 2019;18(1):176. doi: 10.1186/s12943-019-1109-9. PMID: 31801551; PMCID: PMC6892141.
  18. Urtishak KA, Wang LS, Culjkovic-Kraljacic B, Davenport JW, Porazzi P, Vincent TL, et al. Targeting EIF4E signaling with ribavirin in infant acute lymphoblastic leukemia. 2019;38(13):2241-62. doi: 10.1038/s41388-018-0567-7. PMID: 30478448; PMCID: PMC6440839.
  19. Shi F, Len Y, Gong Y, Shi R, Yang X, Naren D, et al. Ribavirin inhibits the activity of mTOR/eIF4E, ERK/Mnk1/eIF4E signaling pathway and synergizes with tyrosine kinase inhibitor Imatinib to impair Bcr-Abl mediated proliferation and apoptosis in Ph+ leukemia. PLoS One. 2015;10(8):e0136746. doi: 10.1371/journal.pone.0136746. PMID: 26317515; PMCID: PMC4552648.
  20. Osborne MJ, Borden KL. The eukaryotic translation initiation factor eIF4E in the nucleus: taking the road less traveled. Immunol Rev. 2015;263(1):210-23. doi: 10.1111/imr.12240. PMID: 25510279; PMCID: PMC4269245.
  21. Xu M, Tao Z, Wang S, Jiang Y, Qu M. Suppression of oncogenic protein translation via targeting eukaryotic translation initiation factor 4E overcomes chemo-resistance in nasopharyngeal carcinoma. Biochem Biophys Res Commun. 2019;512(4):902-7. doi: 10.1016/j.bbrc.2019.03.118. PMID: 30929914.
  22. De Rubis G, Paudel KR, Yeung S, Agarwal V, Hansbro PM, Oliver BGG, et al. Ribavirin attenuates carcinogenesis by downregulating IL-6 and IL-8 in vitro in human lung adenocarcinoma. Pathol Res Pract. 2024;253:155038. doi: 10.1016/j.prp.2023.155038. PMID: 38101157.
  23. pubChem [Internet]. Bethesda (MD): National Library of Medicine (US), National Center for Biotechnology Information; 2004-. PubChem Compound Summary for CID 35370, Zidovudine; [cited at: 2024 Nov. 28]. Available from: https://pubchem.ncbi.nlm.nih.gov/compound/Zidovudine
  24. Oliveira Rocha AM, Severo Sabedra Sousa F, Mascarenhas Borba V, S Munchen T, Guerin Leal J, Dorneles Rodrigues OE, et al. Evaluation of the effect of synthetic compounds derived from azidothymidine on MDA-MB-231 type breast cancer cells. Bioorg Med Chem Lett. 2020;30(17):127365. doi: 10.1016/j.bmcl.2020.127365. PMID: 32738968.
  25. Zhang C, Xu C, Gao X, Yao Q. Platinum-based drugs for cancer therapy and anti-tumor strategies. 2022;12(5):2115-32. doi: 10.7150/thno.69424. PMID: 35265202; PMCID: PMC8899578.
  26. Sabokrouh A, Vaisi-Raygani A, Goodarzi MT, Khatami S, Taghizadeh-Jahed M, Shahabadi N, et al. Comparison between platinum-azidothymidine and azidothymidine effects on Bcl-2 and telomerase gene expression in rats with hepatocellular carcinoma. Avicenna J Med Biotechnol. 2015;7(2):50-6. PMID: 26140181; PMCID: PMC4483314.
  27. Romani AMP. Cisplatin in cancer treatment. Biochem Pharmacol. 2022;206:115323. doi: 10.1016/j.bcp.2022.115323. PMID: 36368406.
  28. Yang Q, Sun Y, Qiu B, Zhao H. FBXW7 Enhances cisplatin-induced apoptosis in oral cancer cell lines. Int Dent J. 2023;73(5):620-7. doi: 10.1016/j.identj.2022.11.008. PMID: 36481094; PMCID: PMC10509406.
  29. Shu XL, Fan CB, Long B, Zhou X, Wang Y. The anti-cancer effects of cisplatin on hepatic cancer are associated with modulation of miRNA-21 and miRNA-122 expression. Eur Rev Med Pharmacol Sci. 2016;20(21):4459-65. PMID: 27874954.
  30. Roake CM, Artandi SE. Regulation of human telomerase in homeostasis and disease. Nat Rev Mol Cell Biol. 2020;21(7):384-97. doi: 10.1038/s41580-020-0234-z. PMID: 32242127; PMCID: PMC7377944.
  31. Wang S, Yang Y, Sun L, Qiao G, Song Y, Liu B. Exosomal MicroRNAs as liquid biopsy biomarkers in hepatocellular carcinoma. Onco Targets Ther. 2020;13:2021-30. doi: 10.2147/OTT.S232453. PMID: 32210570; PMCID: PMC7069575.
  32. Cao F, Yin LX. miR-122 enhances sensitivity of hepatocellular carcinoma to oxaliplatin via inhibiting MDR1 by targeting Wnt/β-catenin pathway. Exp Mol Pathol. 2019;106:34-43. doi: 10.1016/j.yexmp.2018.10.009. PMID: 30539797.
  33. Godbole M, Chandrani P, Gardi N, Dhamne H, Patel K, Yadav N, et al. miR-129-2 mediates down-regulation of progesterone receptor in response to progesterone in breast cancer cells. Cancer Biol Ther. 2017;18(10):801-5. doi: 10.1080/15384047.2017.1373216. PMID: 28876975; PMCID: PMC5678702.
  34. Judasz E, Lisiak N, Kopczyński P, Taube M, Rubiś B. The role of telomerase in breast cancer's response to therapy. Int J Mol Sci. 2022;23(21):12844. doi: 10.3390/ijms232112844. PMID: 36361634; PMCID: PMC9654063.
  35. Lipinska N, Romaniuk A, Paszel-Jaworska A, Toton E, Kopczynski P, Rubis B. Telomerase and drug resistance in cancer. Cell Mol Life Sci. 2017;74(22):4121-32. doi: 10.1007/s00018-017-2573-2. PMID: 28623509; PMCID: PMC5641272.
  36. Zhang Z, Yu L, Dai G, Xia K, Liu G, Song Q, et al. Telomerase reverse transcriptase promotes chemoresistance by suppressing cisplatin-dependent apoptosis in osteosarcoma cells. Sci Rep. 2017;7(1):7070. doi: 10.1038/s41598-017-07204-w. PMID: 28765565; PMCID: PMC5539325.
Middle East Journal of Cancer

Articles in Press, Accepted Manuscript
Available Online from 21 January 2025
Files
Share
How to cite
Statistics