Volume 33, Issue 10 (January 2023)                   Studies in Medical Sciences 2023, 33(10): 720-727 | Back to browse issues page


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PhD in toxicology, Department of Pharmacology and Toxicology, Faculty of pharmacy, Mazandaran university of Medical Sciences, Sari, Iran (Corresponding Author) , farzaneh.motafegh@gmail.com
Abstract:   (1083 Views)
Background & Aim: Cancer is one of the serious health problems of today's societies, and extensive efforts are being made to deal with it. Nevertheless, in many cases, cancer cells can finally deal with the provided treatment solutions and even sometimes, with the emergence of resistance to chemotherapy, they can benefit from the treatments used for faster tumor growth. Currently, there are several specific CDK4/6 inhibitors such as Palbociclib, Ribociclib, Abemaciclib, and these specific inhibitors significantly reduce tumorigenesis, growth, and tumor invasion. The aim of this study was to investigate the cytotoxicity of Abemaciclib drug on the growth rate and ROS production in two cancer cell lines, A549 and AGS.
Materials & Methods: In this experimental study, AGS (gastric cancer) and 549A (lung cancer) cell lines were cultured. Cell viability was measured by MTT test and oxygen free radical production rate by ROS test to check the sensitivity of Abemaciclib drug in doses of 1, 2.5, 5, 10, 20 μM in specified cell lines. The data was analyzed with Graph Pad Prism v.:8 software and P<0.05 was considered as a significant level.
Findings: The findings of this study show that Abemaciclib can be used as a therapeutic agent in these two cancers, because with the increase in drug concentration, the growth of the target cancer cells decreased.
Discussion: The results obtained from this study showed that Abemaciclib significantly reduced cell survival and proliferation in (549A) and (AGS) cell lines compared to the control at doses of 10 and 20 μM. More laboratory and animal studies are needed to investigate the exact molecular and clinical processes of Abemaciclib.
 
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Type of Study: Research | Subject: Poisoning

References
1. Kim ES. Abemaciclib: first global approval. Drugs 2017;77:2063-70. https://doi.org/10.1007/s40265-017-0825-y https://doi.org/10.1007/s40265-017-0770-9 https://doi.org/10.1007/s40265-017-0813-2 https://doi.org/10.1007/s40265-017-0840-z https://doi.org/10.1007/s40265-017-0749-6 [DOI:10.1007/s40265-017-0779-0]
2. Torre LA, Bray F, Siegel RL, Ferlay J, Lortet‐Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin 2015;65(2):87-108. [DOI:10.3322/caac.21262] [PMID]
3. Ahmad OB, Boschi-Pinto C, Lopez AD, Murray CJ, Lozano R, Inoue M. Age standardization of rates: a new WHO standard. Geneva: World Health Organization 2001;9(10):1-14. [Google Scholar]
4. Dong SQ, Singh TP, Wei X, Yao H, Wang HL. a Japanese population‐based meta‐analysis of vonoprazan versus PPI for Helicobacter pylori eradication therapy: is superiority an illusion? Helicobacter 2017;22(6):e12438. [DOI:10.1111/hel.12438] [PMID]
5. Jameson JL, Fauci AS, Kasper DL, Hauser SL, Longo DL, Loscalzo J. Harrison's principles of internal medicine. 2018. [URL]
6. Allegri L, Baldan F, Mio C, Puppin C, Russo D, KRYšTOF V, et al. Effects of BP-14, a novel cyclin-dependent kinase inhibitor, on anaplastic thyroid cancer cells. Oncol Rep 2016;35(4):2413-8. [DOI:10.3892/or.2016.4614] [PMID]
7. Roskoski Jr R. Cyclin-dependent protein kinase inhibitors including palbociclib as anticancer drugs. Pharmacol Res 2016;107:249-75. [DOI:10.1016/j.phrs.2016.03.012] [PMID]
8. Lee HJ, Lee WK, Kang CW, Ku CR, Cho YH, Lee EJ. A selective cyclin-dependent kinase 4, 6 dual inhibitor, Ribociclib (LEE011) inhibits cell proliferation and induces apoptosis in aggressive thyroid cancer. Cancer Lett 2018;417:131-40. [DOI:10.1016/j.canlet.2017.12.037] [PMID]
9. Hamilton E, Infante JR. Targeting CDK4/6 in patients with cancer. Cancer Treat Rev 2016;45:129-38. [DOI:10.1016/j.ctrv.2016.03.002] [PMID]
10. Otto T, Sicinski P. Cell cycle proteins as promising targets in cancer therapy. Nat Rev Cancer 2017;17(2):93-115. [DOI:10.1038/nrc.2016.138] [PMID] [PMCID]
11. Motafeghi F, Shokrzadeh M, Mortazavi P, Habibi E. Evaluation of the cytotoxic effect of the tarragon (Artemisia dracunculus L.) hydroalcoholic extract on the HT-29, MKN45, and MCF-7 cell lines. Pharm Biomed Res 2023;9(1):0-. [DOI:10.32598/PBR.9.1.1025.2]
12. Motafeghi F, Gerami M, Mortazavi P, Khayambashi B, Ghassemi-Barghi N, Shokrzadeh M. Green synthesis of silver nanoparticles, graphene, and silver-graphene nanocomposite using Melissa officinalis ethanolic extract: Anticancer effect on MCF-7 cell line. Iranian Journal of Basic Med Sci 2023;26(1). [Google Scholar]
13. Shokrzadeh M, Mortazavi P, Moghadami A, Khayambashi B, Motafeghi F. Synergistic Antiproliferative and Anticancer Activity of Carotenoid Lutein or Coenzyme Q10 in Combination with Doxorubicin on the MCF7 Cell Line. App InVitro Toxicol 2021;7(4):167-74. [DOI:10.1089/aivt.2021.0008]
14. Motafeghi F, Shahsavari R, Mortazavi P, Shokrzadeh M. Anticancer effect of paroxetine and amitriptyline on HT29 and A549 cell lines. Toxicol InVitro 2022:105532. [DOI:10.1016/j.tiv.2022.105532] [PMID]
15. Motafeghi F, Mortazavi P, Mahdavi M, Shokrzadeh M. Cellular effects of epsilon toxin on the cell viability and oxidative stress of normal and lung cancer cells. Microb Pathog 2022:105649. [DOI:10.1016/j.micpath.2022.105649] [PMID]
16. Motafeghi F, Khayambashi B, Mortazavi P, Eghbali M, Salmanmahiny A, Shahsavari R, et al. Synergistic Effect of Selenium/Zinc with Sulfasalazine on the Human Colorectal Cancer Cell Line (HT-29). App InVitro Toxicol 2022. [DOI:10.1089/aivt.2022.0007]
17. Motafeghi F, Mortazavi P, Salman Mahiny AH, Abtahi MM, Shokrzadeh M. The role of ginger's extract and N-acetylcysteine against docetaxel-induced oxidative stress and genetic disorder. Drug Chem Toxicol 2022:1-8. [DOI:10.1080/01480545.2022.2075377] [PMID]
18. Motafeghi F, Mortazavi P, Ghassemi-Barghi N, Zahedi M, Shokrzadeh M. Dexamethasone as an anti-cancer or Hepatotoxic. Toxicol Mech Methods 2022:1-17. [DOI:10.1080/15376516.2022.2105183] [PMID]
19. Christiansen H. Ergebnisse der Radiotherapie beim anaplastischen Schilddrüsenkarzinom. [Google Scholar]
20. Sanchez-Martinez C, Gelbert LM, Lallena MJ, de Dios A. Cyclin dependent kinase (CDK) inhibitors as anticancer drugs. Bioorg Med Chem Lett 2015;25(17):3420-35. [DOI:10.1016/j.bmcl.2015.05.100] [PMID]
21. Bonavida B, Chen Z-S, Yang D-H. Protein Kinase Inhibitors as Sensitizing Agents for Chemotherapy: Academic Press; 2018. [URL]
22. Naoum GE, Morkos M, Kim B, Arafat W. Novel targeted therapies and immunotherapy for advanced thyroid cancers. Mol Cancer 2018;17(1):1-15. [DOI:10.1186/s12943-018-0786-0] [PMID] [PMCID]
23. Denaro N, Nigro CL, Russi EG, Merlano MC. The role of chemotherapy and latest emerging target therapies in anaplastic thyroid cancer. OncoTargets Ther 2013:1231-41. [DOI:10.2147/OTT.S46545] [PMID] [PMCID]
24. Asghar U, Witkiewicz AK, Turner NC, Knudsen ES. The history and future of targeting cyclin-dependent kinases in cancer therapy. Nat Rev Drug Discovery 2015;14(2):130-46. [DOI:10.1038/nrd4504] [PMID] [PMCID]
25. Chen S, Gong X, Zhang Y, Van Horn R, Yin T, Huber L, et al. RAF inhibitor LY3009120 sensitizes RAS or BRAF mutant cancer to CDK4/6 inhibition by abemaciclib via superior inhibition of phospho-RB and suppression of cyclin D1. Oncogene 2018;37(6):821-32. [DOI:10.1038/onc.2017.384] [PMID]
26. Torres-Guzmán R, Calsina B, Hermoso A, Baquero C, Alvarez B, Amat J, et al. Preclinical characterization of abemaciclib in hormone receptor positive breast cancer. Oncotarget 2017;8(41):69493. [DOI:10.18632/oncotarget.17778] [PMID] [PMCID]
27. Dickler MN, Tolaney SM, Rugo HS, Cortés J, Diéras V, Patt D, et al. MONARCH 1, A Phase II Study of Abemaciclib, a CDK4 and CDK6 Inhibitor, as a Single Agent, in Patients with Refractory HR+/HER2− Metastatic Breast CancerPhase II Study of Abemaciclib in HR+/HER2− MBC. Clin Cancer Res 2017;23(17):5218-24. [DOI:10.1158/1078-0432.CCR-17-0754] [PMID] [PMCID]
28. Sledge Jr GW, Toi M, Neven P, Sohn J, Inoue K, Pivot X, et al. MONARCH 2: abemaciclib in combination with fulvestrant in women with HR+/HER2− advanced breast cancer who had progressed while receiving endocrine therapy. J Clin Oncol 2017;35(25):2875-84. [DOI:10.1200/JCO.2017.73.7585] [PMID]
29. Iriyama N, Hino H, Moriya S, Hiramoto M, Hatta Y, Takei M, et al. The cyclin-dependent kinase 4/6 inhibitor, abemaciclib, exerts dose-dependent cytostatic and cytocidal effects and induces autophagy in multiple myeloma cells. Leukemia Lymphoma 2018;59(6):1439-50. [DOI:10.1080/10428194.2017.1376741] [PMID]
30. Tate SC, Sykes AK, Kulanthaivel P, Chan EM, Turner PK, Cronier DM. A population pharmacokinetic and pharmacodynamic analysis of abemaciclib in a phase I clinical trial in cancer patients. Clin Pharmacokinetics 2018;57:335-44. [DOI:10.1007/s40262-017-0559-8] [PMID] [PMCID]
31. Fujiwara Y, Tamura K, Kondo S, Tanabe Y, Iwasa S, Shimomura A, et al. Phase 1 study of abemaciclib, an inhibitor of CDK 4 and 6, as a single agent for Japanese patients with advanced cancer. Cancer Chemother Pharmacol 2016;78:281-8. [DOI:10.1007/s00280-016-3085-8] [PMID]
32. Kempf E, Rousseau B, Besse B, Paz-Ares L. KRAS oncogene in lung cancer: focus on molecularly driven clinical trials. Eur Resp Rev 2016;25(139):71-6. [DOI:10.1183/16000617.0071-2015] [PMID] [PMCID]
33. Wu T, Chen Z, To KK, Fang X, Wang F, Cheng B, et al. Effect of abemaciclib (LY2835219) on enhancement of chemotherapeutic agents in ABCB1 and ABCG2 overexpressing cells in vitro and in vivo. Biochem Pharmacol 2017;124:29-42. [DOI:10.1016/j.bcp.2016.10.015] [PMID]

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