Necroptosis Triggered by Ros Accumulation and Ca2+ Overload, Partly Explains the Inflammatory Responses and Anti-Cancer Effects Associated With 1Hz, 100 Mt Elf-Mf in Vivo

Necroptosis Triggered by Ros Accumulation and Ca2+ Overload, Partly Explains the Inflammatory Responses and Anti-Cancer Effects Associated With 1Hz, 100 Mt Elf-Mf in Vivo Publisher Pubmed

Barati M¹ ; Javidi MA¹ ; Darvishi B² ; Shariatpanahi SP³ ; Mesbah Moosavi ZS⁴ ; Ghadirian R¹ ; Khani T¹ ; Sanati H⁵ ; Simaee H¹ ; Shokrollahi Barough M⁵ ; Farahmand L² ; Madjid Ansari A¹

Show Affiliations

1. Integrative Oncology Department, Breast Cancer Research Center, Motamed Cancer Institute, ACECR, Tehran, Iran
2. Recombinant Proteins Department, Breast Cancer Research Center, Motamed Cancer Institute, ACECR, Tehran, Iran
3. Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran
4. Muscle Health Research Centre, School of Kinesiology and Health Science, York University, Toronto, ON, Canada
5. ATMP Department, Breast Cancer Research Center, Motamed Cancer Institute, ACECR, Tehran, Iran

Source: Free Radical Biology and Medicine Published:2021

Abstract

Whereas the anti-neoplastic activity of extremely low frequency magnetic fields (ELF-EMF) is well-documented in literature, little is known about its underlying anti-cancer mechanisms and induced types of cell death. Here, for the first time, we reported induction of necroptosis, a specific type of programed necrotic cell death, in MC4-L2 breast cancer cell lines following a 2 h/day exposure to a 100 Hz, 1 mT ELF-EMF for five days. For in vivo assessment, inbred BALB/c mice bearing established MC-4L2 tumors were exposed to 100 mT, 1 Hz ELF-EMF 2 h daily for a period of 28-day, following which tumors were dissected and fixed for evaluation of tumor biomarkers expression and types of cell death induced using TUNEL assay, Immunohistochemistry and H&E staining. Peripheral blood samples were also collected for assessing pro-inflammatory cytokine profile following exposure. An exaggerated proinflammatory response evident form enhancement of IFN-γ (4.8 ± 0.24 folds) and TNF-α (3.1 ± 0.19 folds) and number of tumors infiltrating lymphocytes (TILs), specially CD8+ Th cells (~20 folds), proposed occurrence of necroptosis in vivo. Meanwhile, exposure could effectively suppress tumor growth and expression of Ki-67, CD31, VEGFR2 and MMP-9. In vitro studies on ELF-EMF exposed MC-4L2 cells demonstrated a meaningful increase in phosphorylation of RIPK1/RIPK3/MLKL proteins and cleavage of caspase-9/caspase-3, confirming occurrence of both necroptosis and apoptosis. Complementary in vitro studies by treating ELF-EMF exposed MC-4L2 cells with verapamil (a calcium channel inhibitor), N-acetyl cysteine (a ROS scavenger) or calcium chloride confirmed the role of elevated intracellular calcium and ROS levels in ELF-EMF induced necroptosis. © 2021 Elsevier Inc.

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Experts (# of related papers)

Mohsen Amin (1)

Style	Citing Format
MLA	Barati M, et al.. "Necroptosis Triggered by Ros Accumulation and Ca2+ Overload, Partly Explains the Inflammatory Responses and Anti-Cancer Effects Associated With 1Hz, 100 Mt Elf-Mf in Vivo." Free Radical Biology and Medicine, vol. 169, no. , 2021, pp. 84-98.
APA	Barati M, Javidi MA, Darvishi B, Shariatpanahi SP, Mesbah Moosavi ZS, Ghadirian R, Khani T, Sanati H, Simaee H, Shokrollahi Barough M, Farahmand L, Madjid Ansari A (2021). Necroptosis Triggered by Ros Accumulation and Ca2+ Overload, Partly Explains the Inflammatory Responses and Anti-Cancer Effects Associated With 1Hz, 100 Mt Elf-Mf in Vivo. Free Radical Biology and Medicine, 169(), 84-98.
Chicago	Barati M, Javidi MA, Darvishi B, Shariatpanahi SP, Mesbah Moosavi ZS, Ghadirian R, Khani T, et al.. "Necroptosis Triggered by Ros Accumulation and Ca2+ Overload, Partly Explains the Inflammatory Responses and Anti-Cancer Effects Associated With 1Hz, 100 Mt Elf-Mf in Vivo." Free Radical Biology and Medicine 169, no. (2021): 84-98.
Harvard	Barati M et al. (2021) 'Necroptosis Triggered by Ros Accumulation and Ca2+ Overload, Partly Explains the Inflammatory Responses and Anti-Cancer Effects Associated With 1Hz, 100 Mt Elf-Mf in Vivo', Free Radical Biology and Medicine, 169(), pp. 84-98.
Vancouver	Barati M, Javidi MA, Darvishi B, Shariatpanahi SP, Mesbah Moosavi ZS, Ghadirian R, et al.. Necroptosis Triggered by Ros Accumulation and Ca2+ Overload, Partly Explains the Inflammatory Responses and Anti-Cancer Effects Associated With 1Hz, 100 Mt Elf-Mf in Vivo. Free Radical Biology and Medicine. 2021;169():84-98.
BibTex	@article{ author = {Barati M and Javidi MA and Darvishi B and Shariatpanahi SP and Mesbah Moosavi ZS and Ghadirian R and Khani T and Sanati H and Simaee H and Shokrollahi Barough M and Farahmand L and Madjid Ansari A}, title = {Necroptosis Triggered by Ros Accumulation and Ca2+ Overload, Partly Explains the Inflammatory Responses and Anti-Cancer Effects Associated With 1Hz, 100 Mt Elf-Mf in Vivo}, journal = {Free Radical Biology and Medicine}, volume = {169}, number = {}, pages = {84-98}, year = {2021} }
RIS	TY - JOUR AU - Barati M AU - Javidi MA AU - Darvishi B AU - Shariatpanahi SP AU - Mesbah Moosavi ZS AU - Ghadirian R AU - Khani T AU - Sanati H AU - Simaee H AU - Shokrollahi Barough M AU - Farahmand L AU - Madjid Ansari A TI - Necroptosis Triggered by Ros Accumulation and Ca2+ Overload, Partly Explains the Inflammatory Responses and Anti-Cancer Effects Associated With 1Hz, 100 Mt Elf-Mf in Vivo JO - Free Radical Biology and Medicine VL - 169 IS - SP - 84 EP - 98 PY - 2021 ER -

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