Low-Frequency Magnetic Fields (LF-MFs) Inhibit Proliferation by Triggering Apoptosis and Altering Cell Cycle Distribution in Breast Cancer Cells.

Aoshu Xu,Tingting Lin,Qian Wang

doi:10.3390/ijms21082952

Abstract

Breast cancer is a common malignancy threatening women’s health around the world. Despite improved treatments for different subtypes of breast tumors that have been put forward, there still exists a poor therapeutic response and prognosis. Magnetic fields, as a non-invasive therapy, have shown anti-tumor effects in vitro and in vivo; however, the detailed mechanisms involved are still not clear. In this study, we found that in exposure to low-frequency magnetic fields (LF-MFs) with an intensity of 1 mT and frequencies of 50, 125, 200, and 275 Hz, separately, the proliferation of breast cancer cells was inhibited and LF-MF with 200 Hz reached the optimum inhibition effect, on exposure time-dependently. Notably, we found that exposure to LF-MF led to MCF-7 and ZR-75-1 cell apoptosis and cell cycle arrest. Moreover, we also discovered that LF-MF effectively increased the level of reactive oxygen species (ROS), suppressed the PI3K/AKT signaling pathway, and activated glycogen synthase kinase-3β (GSK-3β). We demonstrated that the GSK3β activity contributed to LF-MF-induced cell proliferation inhibition and apoptosis, while the underlying mechanism was associated with the inhibition of PI3K/AKT through increasing the intracellular ROS accumulation. These results indicate that LF-MF with a specific frequency may be an attractive therapy to treat breast cancers.

Highlights

Breast cancer is a malignant tumor that often occurs in females, accounting for 7–10% of all systemic malignant tumors, which seriously affect the physical and mental health of women [1]
Compared to the group with single exposure to Magnetic field (MF), the expressions of p-PI3K and p-AKT were upregulated after MF+NAC treatment, which suggested that NAC reversed the MF-induced inactivation of the PI3K/AKT signaling pathway. These findings indicate that low-frequency magnetic fields (LF-MFs) suppressed the activation of PI3K/AKT signaling pathways by reactive oxygen species (ROS) accumulation
The expression levels of p-glycogen synthase kinase-3β (GSK-3β) (Ser 9) in MCF-7 and ZR75-1 cells were remarkably downregulated after LF-MF exposure, implying the activation of GSK-3β, whereas this effect was partly reversed by PI3K/AKT activator IGF-1 and specific GSK-3β inhibitor CHIR-99021. These findings indicate that LF-MF promoted the activation of GSK-3β through the inactivation of PI3K/AKT

Summary

Introduction

Breast cancer is a malignant tumor that often occurs in females, accounting for 7–10% of all systemic malignant tumors, which seriously affect the physical and mental health of women [1]. The age of onset has tended to be younger, and the tumors themselves are highly heterogeneous with a high mortality rate [2]. It is of great significance to find a novel, general and more efficient treatment therapy for breast cancers. Magnetic field (MF) therapy has been put forward as a non-invasive and safe approach to cancer, which has the advantage of a high efficiency and low cost, without inducing infections or forming scars [4]. Further research has found that low-frequency magnetic fields (LF-MFs), namely, those with a frequency below 300 Hz, possess a variety of effects such as the regulation of immunity [10] and inflammation [11], suppression of angiogenesis [12], contribution to differentiation [13], and induced apoptosis [14]. Many biological effects of magnetic fields have been reported, the mechanisms involved still remain unclear

Methods

Results

Conclusion