Radiofrequency Electromagnetic Fields Cause Non-Temperature-Induced Physical and Biological Effects in Cancer Cells

SIMPLE SUMMARY: Radiofrequency electromagnetic fields are used for tumor heating as adjunct therapy, but it appears that sufficient temperatures can sometimes not be reached. We therefore aimed to study potential non-temperature-induced anticancer effects when adding amplitude modulation to the radiofrequency waves. We could demonstrate in a colorectal cancer model that radiofrequency electromagnetic fields do have anticancer effects when not being induced by increased temperature that can be further increased by amplitude modulation. Therefore, this treatment could potentially serve as a more effective tumor therapy. ABSTRACT: Non-temperature-induced effects of radiofrequency electromagnetic fields (RF) have been controversial for decades. Here, we established measurement techniques to prove their existence by investigating energy deposition in tumor cells under RF exposure and upon adding amplitude modulation (AM) (AMRF). Using a preclinical device LabEHY-200 with a novel in vitro applicator, we analyzed the power deposition and system parameters for five human colorectal cancer cell lines and measured the apoptosis rates in vitro and tumor growth inhibition in vivo in comparison to water bath heating. We showed enhanced anticancer effects of RF and AMRF in vitro and in vivo and verified the non-temperature-induced origin of the effects. Furthermore, apoptotic enhancement by AM was correlated with cell membrane stiffness. Our findings not only provide a strategy to significantly enhance non-temperature-induced anticancer cell effects in vitro and in vivo but also provide a perspective for a potentially more effective tumor therapy.