The antitumor effect of static and extremely low frequency magnetic fields against nephroblastoma and neuroblastoma

Abstract

Certain magnetic fields (MF) have potential therapeutic antitumor effect whereas the underlying mechanism remains undefined. In this study, a well-characterized MF was applied to two common childhood malignancies, nephroblastoma and neuroblastoma. This MF has a time-averaged total intensity of 5.1 militesla (mT), and was generated as a superimposition of a static and an extremely low frequency (ELF) MF in 50 Hertz (Hz). In nephroblastoma and neuroblastoma cell lines including G401, CHLA255, and N2a, after MF exposure of 2 h per day, the cell viability decreased significantly after 2 days. After 3 days, inhibition rates of 17-22% were achieved in these cell lines. Furthermore, the inhibition rate was positively associated with exposure time. On the other hand, when using static MF only while maintaining the same time-averaged intensity of 5.1 mT, the inhibition rate was decreased. Thus, both time and combination of ELF field were positively associated with the inhibitory effect of this MF. Exposure to the field decreased cell proliferation and induced apoptosis. Combinational use of MF together with chemotherapeutics cisplatin (DDP) was performed in both in vitro and in vivo experiments. In cell lines, combinational treatment further increased the inhibition rate compared with single use of either DDP or MF. In G401 nephroblastoma tumor model in nude mice, combination of MF and DDP resulted in significant decrease of tumor mass, and the side effect was limited in mild liver injury. MF exposure by itself did not hamper liver or kidney functions. In summary, the antitumor effect of an established MF against neuroblastoma and nephroblastoma is reported, and this field has the potential to be used in combination with DDP to achieve increased efficacy and reduce side effects in these two childhood malignancies. Bioelectromagnetics. 39:375-385, 2018. © 2018 Wiley Periodicals, Inc.

Induction of apoptosis and ferroptosis by a tumor suppressing magnetic field through ROS-mediated DNA damage

“…Previously in our lab, G401 nephroblastoma xenograft has been successfully established in nude mice. The tumor was fairly resistant to DDP, and MF sensitized the tumor to DDP treatment [17]. In this study, occurrence of DNA damage and activation of repair has also been confirmed in tumor xenografts.…”

“…In this study, a previously reported tumor suppressing field [17] has been further shown to selectively inhibit several types of cancer cells. Similarly in another study, a 50 Hz field with a flux density of 1 mT induced apoptosis in a transformed human squamous cell carcinoma line, but not in a non-transformed human amniotic fluid cell line [11].…”

“…Such examples include ELF-MF in combination with DDP or 5-FU [20,21], SMF with doxorubicin [22], and pulsed EMF with daunorubicin [23]. We have previously reported the sensitizing effect of this tumor suppressing MF to DDP treatment in nephroblastoma [17]. In this study, this field is further shown to sensitize tumor cells to both antimetabolite drugs (5-FU, DDP) and antimitotic drugs (VCR and PTX), with different potency in different cell lines, suggesting the field could potentially be applied as adjuvant to conventional chemotherapies.…”

“…In our previous studies, a 50 Hz ELF-EMF modulated by SMF with a time-averaged intensity of 5.1 militesla (mT), has been shown to inhibit the proliferation of nephroblastoma and neuroblastoma cells, and to sensitize the tumors to conventional chemotherapy [17]. A similar modulated field was previously found to promote apoptosis in breast cancer and colon adenocarcinoma [3,18].…”

“…A self-constructed MF exposure facility was used in this study, based on a prototype previously established [3]. The characteristics of the MF generated by this facility were published previously [17]. Briefly, modulated MF was generated by a pair of coils mounted horizontally with their axes lying along the same plane and orthogonally to the ground.…”