Pivotal Factors in Breast Cancer Molecular Subtypes Apoptosis Induction by Elf-Emf; Ki-67, Ros Level, Her-2, and Sods Publisher Pubmed



Shayeghan M ; Shahriari F ; Afroughi F ; Forouzesh F ; Niakan M H ; Javidi M A
Source: Breast Journal Published:2026

Abstract

Background: Although increasing research has shown that extremely low-frequency electromagnetic fields (ELF-EMFs) specifically trigger PCD through the elevation of ROS levels in cancer cells, there is no adequate evidence to determine the exact mechanisms of this phenomenon. The antioxidant machinery may play a crucial role in this area; however, this has been neglected in previous research. Methods: The main aim of this study was to assess the effect of ELF-EMF exposure (5 days, 1 Hz, 100 mT, 2 h/day) on ROS levels, expression levels of antioxidant genes, and apoptosis induction in different breast cancer molecular subtypes with different p53 statuses. Results: DCFH-DA results revealed that the ROS level increased in all three cell lines (SKBR-3, MDA-MB-231, and MCF-7); this increase was much greater in SKBR-3 (up to 5-fold compared to its sham exposure). This result was concurrent with the annexin V/PI results; SKBR-3 cells showed much more apoptosis induction (about 78%), compared with the others (22% or 11% in the other two cells). On the other hand, the mRNA expression level of SOD1 and SOD2 increased significantly in the MDA-MB-231, in addition to these two genes, the expression level of SOD3 and GSR increased in the MCF-7 cells but not in the SKBR-3. Conclusion: Taken together, our results confirmed that ELF-EMF induced ROS-dependent apoptosis, especially in HER-2-enriched breast cancer cells (the SKBR-3), in a p53-independent manner. Other molecular subtypes (MDA-MB-231 as TNBC, or MCF-7 as luminal A) showed resistance against the ROS level increasing and subsequent apoptosis induction by using antioxidant genes, especially SOD1. Copyright © 2026 Mohadeseh Shayeghan et al. The Breast Journal published by John Wiley & Sons Ltd.