اثر متوپرولول بر فعالیت حیاتی سلولهای سرطانی خون انسان

نوع مقاله : مقاله پژوهشی

نویسندگان

گروه ایمنی شناسی، دانشکده پزشکی، دانشگاه شاهد، تهران، ایران

چکیده

مقدمه و هدف: : متوپرولول به‌عنوان یک بتابلوکر، کاربرد فراوانی در درمان برخی بیماری‌های قلبی از جمله فشار خون و انفارکتوس دارد. اثرات سیتوتوکسیک، ضدالتهابی و ضدتوموری متوپرولول گزارش شده‌اند. هدف این مطالعه بررسی اثر متوپرولول بر فعالیت حیاتی رده‌های سلولی سرطانی خون انسان است.
مواد و روش ها: سلول‌های سرطانی خون انسان MOLT-4)  JURKAT, و (U937  در محیطRPMI  کامل کشت داده شدند و سپس به تعداد well /cell  104´3 در گروه‌های پنج چاهکی درون پلیت‌های کشت 96 چاهکی در محیط کشت RPMI حاوی FCS 10% تحت تیمار با غلظت‌های مختلف متوپرولول (μg/ml 1000- 1) در فواصل زمانی 24، 48 و 72 ساعت قرار گرفتند. نهایتاً فعالیت حیاتی سلول‌ها با روش رنگ‌آمیزی تریپان بلو بررسی شد. نتایج حاصله بین گروه تست و کنترل با آزمون آنالیز واریانس مورد مقایسه قرار گرفت.
نتایج: فعالیت حیاتی هر سه رده سلولی پس از 48 ساعت تیمار در مجاورت غلظتμg/ml   1000 از متوپرولول به‌طور معنا‌داری در مقایسه با کنترل کاهش یافت. متوپرولول پس از 72 ساعت تیمار، فعالیت حیاتی دو رده
 MOLT-4 وJURKAT را در غلظت μg/ml 100³ و رده U937 را در غلظت μg/ml 500³ به‌طور معنا‌داری در مقایسه با کنترل کاهش داد.
نتیجه‌گیری: متوپرولول فعالیت حیاتی رده‌های سلولی سرطان خون انسان را به‌صورت وابسته به غلظت و زمان کاهش می‌دهد. اثرات ضدتوموری متوپرولول ممکن است تا حدی ناشی از کاهش فعالیت حیاتی سلول‌ها توسط این دارو باشد؛ بنابراین متوپرولول می‌تواند برای درمان سرطان خون کاربرد بالقوه داشته باشد.

کلیدواژه‌ها

موضوعات


عنوان مقاله [English]

Effect of metoprolol on viability of human blood cancerous cells

نویسندگان [English]

  • Baran Hajatbeigi
  • Fatemeh Hajghasemi
Department of Immunology, Faculty of Medicine, Shahed University, Tehran, Iran
چکیده [English]

Background and Objective: Metoprolol as a β-Blocker is widely used in treatment of some cardiovascular diseases such as hypertension and myocardial infarction. Moreover, cytotoxic, anti-inflammation, anti-angiogenic and anti-tumor effects of metoprolol have been reported. The intention of this study was to examine metoprolol effect on viability of human blood cancerous cells in vitro.
Materials and Methods: Human leukemic T cells (MOLT-4 and JURKAT) and monocyte (U937) were cultured in Roswell Park Memorial Institute (RPMI) complete medium. Then, the cells (3 ×10 4 cell/well) were treated with different concentrations of metoprolol (1-1000 μg/ml) for 24, 48 and 72 hours. Finally, the viability of cells was determined using trypan blue dye exclusion assay. Analysis of variance (ANOVA) was used to compare the cell viability between different groups.
Results: Metoprolol significantly decreased the viability of all cell lines at 1000 μg/ml concentration after 48 hours incubation time compared with control group. Besides, metoprolol significantly reduced the viability of MOLT-4 and Jurkat cells at ≥ 100 μg/ml concentrations and U937 ≥ 500 μg/ml after 72 hours incubation time in comparison with control group.
Conclusion: Based on results of the present study, metoprolol decreased viability of human blood cancerous cells dose and time dependently. Therefore, anti-tumoral effects of metoprolol reported by other investigators might be partly due to its reducing the viability of cancerous cells. So, metoprolol may have potential implication in therapy of blood tumors along with other cancers.

کلیدواژه‌ها [English]

  • Metoprolol
  • Viability
  • Leukemia
  1. Escajeda JT, Katz KD, Rittenberger JC. Successful treatment of metoprolol-induced cardiac arrest with high-dose insulin, lipid emulsion, and ECMO. The American Journal of Emergency Medicine. 2015;33(8):1111. e1-. e4.
  2. Ivanova E, Ruzgienė D, Ažukaitis K, Jankauskienė A. Pharmacological Treatment of Arterial Hypertension in Children and Adolescents in Lithuania. Int J Environ Res Public Health. 2022;19(21):13949. 2.
  3. Ozaydin M, Peker O, Erdogan D, Akcay S, Yucel H, Icli A, et al. Oxidative Status, Inflammation, and Postoperative Atrial Fibrillation With Metoprolol vs Carvedilol or Carvedilol Plus N-Acetyl Cysteine Treatment. Clinical Cardiology. 2014;37(5):300-6.
  4. Wang D, Chen Y, Jiang J, Zhou A, Pan L, Chen Q, et al. Carvedilol has stronger anti-inflammation and anti-virus effects than metoprolol in murine model with coxsackievirus B3-induced viral myocarditis. Gene. 2014;547(2):195-201.
  5. Ulleryd MA, Bernberg E, Yang LJ, Bergstrom GM, Johansson ME. Metoprolol reduces proinflammatory cytokines and atherosclerosis in ApoE-/- mice. BioMed Research International. 2014;2014:548783.
  6. Pasquier E, Street J, Pouchy C, Carre M, Gifford A, Murray J, et al. β-blockers increase response to chemotherapy via direct antitumour and anti-angiogenic mechanisms in neuroblastoma. British Journal of Cancer. 2013;108(12):2485.
  7. Sidorova M, Petrikaitė V. The Effect of Beta Adrenoreceptor Blockers on Viability and Cell Colony Formation of Non-Small Cell Lung Cancer Cell Lines A549 and H1299. Molecules. 2022; 27(6):1938.
  8. Zhang D., Ma Q., Shen S., Hu H. Inhibition of pancreatic cancer cell proliferation by propranolol occurs through apoptosis induction: The study of beta-adrenoceptor antagonist’s anticancer effect in pancreatic cancer cell. Pancreas. 2009; 38, 94–100.
  9. Le Bozec A, Brugel M, Djerada Z, Ayad M, Perrier M, Carlier C, Botsen D, Nazeyrollas P, Bouché O, Slimano F. Beta-blocker exposure and survival outcomes in patients with advanced pancreatic ductal adenocarcinoma: a retrospective cohort study (BETAPANC). Front Pharmacol. 2023; 14:1137791.
  10. Ribatti D. Anti-angiogenesis in neuroblastoma. Crit Rev Oncol Hematol. 2013; 86(3): 212-21.
  11. İşeri ÖD, Sahin FI, Terzi YK, Yurtcu E, Erdem SR, Sarialioglu F. beta-Adrenoreceptor antagonists reduce cancer cell proliferation, invasion, and migration. Pharmaceutical Biology. 2014;52(11):1374-81.
  12. Stiles JM, Amaya C, Rains S, Diaz D, Pham R, Battiste J, et al. Targeting of beta adrenergic receptors results in therapeutic efficacy against models of hemangioendothelioma and angiosarcoma. PloS one. 2013;8(3):e60021.
  13. Coelho M, Soares-Silva C, Brandão D, Marino F, Cosentino M, Ribeiro L. β-Adrenergic modulation of cancer cell proliferation: available evidence and clinical perspectives. Journal of cancer Research and Clinical Oncology. 2017;143(2):275-91.
  14. Zhou C, Chen X, Zeng W, Peng C, Huang G, Li Xa, et al. Propranolol induced G0/G1/S phase arrest and apoptosis in melanoma cells via AKT/MAPK pathway. Oncotarget. 2016;7(42):68314.
  15. Watkins JL, Thaker PH, Nick AM, Ramondetta LM, Kumar S, Urbauer DL, et al. Clinical impact of selective and nonselective beta-blockers on survival in patients with ovarian cancer. Cancer. 2015;121(19):3444-51.
  16. Raimondi S, Botteri E, Munzone E, Cipolla C, Rotmensz N, DeCensi A, et al. Use of beta-blockers, angiotensin‐converting enzyme inhibitors and angiotensin receptor blockers and breast cancer survival: Systematic review and meta‐analysis. International Journal of Cancer. 2016;139(1):212-9.
  17. Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer statistics, 2022. CA Cancer J Clin. 2022;72(1):7-33.
  18. Greaves M. Leukaemia 'firsts' in cancer research and treatment. Nature reviews Cancer. 2016;16(3):163-72.
  19. Kantarjian H, Kadia T, DiNardo C, Daver N, Borthakur G, Jabbour E, et. al. Acute myeloid leukemia: current progress and future directions. Blood Cancer J. 2021 Feb 22;11(2):41.
  20. Baumeister J, Chatain N, Sofias AM, Lammers T, Koschmieder S. Progression of Myeloproliferative Neoplasms (MPN): Diagnostic and Therapeutic Perspectives. Cells. 2021;10(12):3551.
  21. Hajighasemi F, Mirshafiey A. In vitro sensitivity of leukemia cells to propranolol. Journal of clinical Medicine Research. 2009;1(3):144.
  22. Cheng SM, Yang SP, Ho LJ, Tsao TP, Chang DM, Lai JH. Carvedilol Modulates In Vitro Granulocyte Macrophage Colony Stimulating Factor Induced Interleukin-10 Production in U937 Cells and Human Monocytes. Immunological Investigations. 2003; 32(1-2):43-58.
  23. Gaeini A, Hajighasemi F. Sensitivity of human leukemic cells to carvedilol. Journal of Basic and Clinical Pathophysiology. 2018;7(1):37-42.
  24. Terlizzi M, Colarusso C, Somma P, De Rosa I, Panico L, Pinto A, Sorrentino R. S1P-Induced TNF-α and IL-6 Release from PBMCs Exacerbates Lung Cancer-Associated Inflammation. Cells. 2022 ;11(16):2524.
  25. Djanani A, Kaneider NC, Meierhofer C, Sturn D, Dunzendorfer S, Allmeier H, Wiedermann CJ. Inhibition of neutrophil migration and oxygen free radical release by metipranolol and timolol. Pharmacology. 2003;68(4):198-203.
  26. Moldéus P, Högberg J, Orrenius S. Isolation and use of liver cells. Methods Enzymol 1978;52:60-71.
  27. Caldwell GW, Masucci JA, Chacon E. High throughput liquid chromatography-mass spectrometry assessment of the metabolic activity of commercially available hepatocytes from 96-well plates. Combinatorial Chemistry and High Throughput Screening. 1999;2:39-51.
  28. Wrobel LJ, Le Gal FA. Inhibition of human melanoma growth by a non-cardioselective β-blocker. Journal of Investigative Dermatology. 2015;135(2):525-31.
  29. Hajighasemi F, Hajighasemi S. Effect of propranolol on angiogenic factors in human hematopoietic cell lines in vitro. Iranian Biomedical Journal. 2009;13(4):223-8.