Çok düşük frekanslı manyetik alan, glioblastomda irinotekan sitotoksisitesini değiştirir: Bir ön gözlem

Amaç: Günlük hayatta kullanılan elektrikli cihazlardan yayılan çok düşük frekanslı elektromanyetik alanlara (ELF-EMF)maruz kalınması, hücresel düzeyde çeşitli değişikliklere neden olabilmektedir. Glioblastoma multiform (GBM), yüksekmortalite ile sonuçlanan agresif bir beyin kanseridir. Tedavi yöntemlerindeki ilerlemelere rağmen, GBM tedaviedilemeyen bir hastalık olarak kalmıştır. Diğer taraftan, GBM hastalarında kullanılan antineoplastik ajanların etkinliğiniazaltabilecek faktörlere karşı önlem alınması da önem kazanmıştır. Antineoplastik bir ajan olan irinotekan, GBM hastalarıiçin kullanılan ilaçlardan biridir. Bu ön çalışmanın amacı, ELF-EMF'nin GBM hücreleri üzerinde irinotekan sitotoksisitesiüzerindeki etkisini incelemektir. Yöntemler: Kontrol grubundaki GBM hücrelerine (U87), farklı konsantrasyonlarda irinotekan (0, 1, 2, 10, 25, 50, 75 ve150 µM) uygulandı. Çalışma grubundaki hücrelere ise, ELF-EMF (50 Hz, 1 mT) ve irinotekan, 1 saat süreyle eş zamanlıuygulandı. Sitotoksisite, XTT testi ile belirlendi. Bulgular: IC50 (yarı-maksimum inhibisyon konsantrasyon) değeri, kontrol grubunda 14,31 µM iken, çalışma grubunda20,51 µM olarak bulundu.Sonuç: Çalışmanın sonuçları, ELF-EMF'nin irinotekanın U87 hücreleri üzerindeki etkinliğini tam olarak bilinmeyen birmekanizma ile azalttığını gösterdi. Bu nedenle, irinotekan ile kemoterapi alan hastaların ELF-EMF'lerden kaçınmak içindaha fazla dikkat göstermeleri gerekmektedir. ELF-EMF'lerin irinotekan sitotoksisitesi üzerindeki etkinliğini hangimekanizmalar aracılığı ortaya koyduğunu göstermek için daha ileri çalışmalara ihtiyaç vardır.

Extremely Low Frequency Magnetic Field Alters Cytotoxicity ofIrinotecan in Glioblastoma: A Preliminary Observation

Objective: Exposure to extremely low-frequency electromagnetic fields (ELF-EMFs) emitted from electric appliances used in daily life may cause various changes at the cellular level. Glioblastoma multiform (GBM) is an aggressive brain cancer resulting in high mortality. Despite advances in treatment methods, GBM has remained an incurable disease. It has become important that necessary precautions are taken to overcome factors that may reduce the efficiency of antineoplastic agents used for GBM patients. Irinotecan, an antineoplastic agent, is one of the second line drugs for GBM patients. The aim of this preliminary research was to examine the impact of ELF-EMF on irinotecan cytotoxicity in GBM cells. Method: GBM cells (U87) in the control group were only treated with irinotecan (0, 1, 2, 10, 25, 50, 75, and 150 µM). ELFEMF (50 Hz, 1 mT) and irinotecan were applied simultaneously for 1 h to similar cells in the study group. Cytotoxicity was determined via XTT assay. Results: While the IC50 (half maximal inhibitory concentration) value was 14.31 µM in the control group, and 20.51 µM in the study group. Conclusion: The results of the study indicated that ELF-EMF reduced the efficiency of irinotecan in the U87 cells. Therefore, patients undergoing chemotherapy with irinotecan should be given more attention so as to avoid ELF-EMFs. The effects of ELF-EMF on irinotecan cytotoxicity in U87 cells were determined through an exactly unknown mechanism. Further studies on ELF-EMFs and irinotecan cytotoxicity are required to illuminate the topic.

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1. Huang X, Wang M, You Q, et al. Synthesis, mechanisms of action, and toxicity of novel aminophosphonates derivatives conjugated irinotecan in vitro and in vivo as potent antitumor agents. Eur J Med Chem. 2020; 189: 112067.
2. Omuro A, De Angelis LM. Glioblastoma and other malignant gliomas: a clinical review. JAMA. 2013; 310: 1842-50.
3. Pommier Y, Leo E, Zhang H, et al. DNA topoisomerases and their poisoning by anticancer and antibacterial drugs. Chem Biol. 2010; 17: 421- 33.
4. Gruber ML, Buster WP. Temozolomide in Combination with Irinotecan for Treatment of Recurrent Malignant Glioma. Am J Cli Oncol. 2004; 27: 33-8.
5. Fujita K, Kubota Y, Ishida H, et al. Irinotecan, a key chemotherapeutic drug for metastatic colorectal cancer. World J Gastroenterol. 2015; 21: 12234-48.
6. Gajšek P, Ravazzani P, Grellier J, et al. Review of Studies Concerning Electromagnetic Field (EMF) Exposure Assessment in Europe: Low Frequency Fields (50 Hz–100 kHz). Int J Environ Res Public Health. 2016; 13: 875.
7. Chang WH, Chen LT, Sun JS, et al. Effect of pulseburst electromagnetic field stimulation on osteoblast cell activities. Bioelectromagnetics. 2004; 25: 457-65.
8. Morgado-Valle C, Verdugo-Diaz L, Garcia DE, et al. The role of voltage-gated Ca2+ channels in neurite growth of cultured chromaffin cells induced by extremely low frequency (ELF) magnetic field stimulation. Cell Tissue Res. 1998; 291: 217-30.
9. Suplizio M, Falone S, Amicarelli F, et al. Molecular basis underlying the biological effects elicited by extremely low-frequency magnetic field (ELF-EMF) on neuroblastoma cells. J Cell Biochem. 2011; 112: 3797-806.
10. Lai C, Singh N. Medical Applications of Electromagnetic Fields. IOP Conf Series. Earth Environ Sci. 2010; 10: 012006.
11. Ruiz Gómez MJ, Pastor Vega JM, de la Peña L, et al. Growth modification of human colon adenocarcinoma cells exposed to a low-frequency electromagnetic field. J Physiol Biochem. 1999; 55: 79-83.
12. Koziorowska A, Romerowicz-Misielak M, Sołek P, et al. Extremely low frequency variable electromagnetic fields affect cancer and noncancerous cells in vitro differently: Preliminary study. Electromagn Biol Med. 2018; 37: 35-42.
13. Ronchetto F, Barone D, Cintorino M, et al. Extremely low frequency-modulated static magnetic fields to treat cancer: A pilot study on patients with advanced neoplasm to assess safety and acute toxicity. Bioelectromagnetics. 2004; 25: 563-71.
14. Pesce M, Patruno A, Speranza L, et al. Extremely low frequency electromagnetic field and wound healing: implication of cytokines as biological mediators. Eur Cytokine Netw. 2013; 24: 1-10.
15. Huang L. Dong L, Chen Y, et al. Effects of sinusoidal magnetic field observed on cell proliferation, ion concentration, and osmolarity in two human cancer cell lines. Electromagn Biol Med. 2006; 25: 113-26.
16. Galluzzi L, Senovilla L, Vitale I, et al. Molecular mechanisms of cisplatin resistance. Oncogene. 2012; 1869-83.
17. Lupke M, Rollwitz J, Simkò M. Cell activating capacity of 50 Hz magnetic fields to release reactive oxygen intermediates in human umbilical cord blood-derived monocytes and in Mono Mac 6 cells. Free Radic Res. 2004; 38: 985-93.
18. Baharara J, Hosseini N, Farzin TR. Extremely low frequency electromagnetic field sensitizes cisplatinresistant human ovarian adenocarcinoma cells via P53 activation. Cytotechnology. 2016; 68: 1403-13.
19. Akbarnejad Z, Eskandary H, Dini L, et al. Cytotoxicity of temozolomide on human glioblastoma cells is enhanced by the concomitant exposure to an extremely low-frequency electromagnetic field (100Hz, 100G). Biomed Pharmacother. 2017; 92: 254-64.
20. Ruiz-Gómez M, De la Peña L, Prieto-Barcia M, et al. Influence of 1 and 25 Hz, 1.5 mT magnetic fields on antitumour drug potency in a human adenocarcinoma cell line. Bioelectromagnetics. 2002; 23: 525-78.
21. Amiri M, Basiri M, EskandaryH, et al. Cytotoxicity of carboplatin on human glioblastoma cells is reduced by the concomitant exposure to an extremely low-frequency electromagnetic field (50 Hz, 70 G). Electromagn Biol Med. 2018; 37: 138-45.
22. Al-Ghafari AB, Punjaruk W, Storer LC, et al. Longterm exposure to irinotecan reduces cell migration in glioma cells. J. Neurooncol. 2016; 127: 455-62.
23. Scientific Committee on Emerging and Newly Identified Health Risks (SCENIHR). Possible effects of electromagnetic fields (EMF) on human health. 2007. http://ec.europa.eu/health/ph_risk/committees/0 4_scenihr/docs/scenihr_mi_007.pdf
24. Batash R, Asna N, Schaffer P, et al. Glioblastoma multiforme, diagnosis and treatment; Recent literature review. Curr Med Chem. 2017; 24: 3002-9.
25. Ge JJ, Li C, Qi SP, et al. Combining therapy with recombinant human endostatin and cytotoxic agents for recurrent disseminated glioblastoma: a retrospective study. BMC Cancer. 2020; 20: 24.
26. Shankayi Z, Firoozabadi S, Mansurian MG. The effect of pulsed magnetic field on the molecular uptake and medium conductivity of leukemia cell. Cell Biochem Biophys. 2013; 65: 211–6.
27. Ross CL, Harrison BS. An introduction to electromagnetic field therapy and immune function: a brief history and current status. J Sci Appl Biomed. 2015; 3: 18-29.
28. Zhou SA, Uesaka M. Bioelectrodynamics in living organisms. Int J Eng Sci. 2006; 44: 67-92.
29. Consales C, Merla C, Marino C, et al. Electromagnetic fields, oxidative stress, and neurodegeneration. Int J Cell Biol. 2012; 16.
30. Steinbeck MJ, Chernets N, Zhang J, et al. Skeletal cell differentiation is enhanced by atmospheric dielectric barrier discharge plasma treatment. PLoS One. 2013; 8: e82143.