Inhibition of Cancer Cell Migration and Glycolysis by Terahertz Wave Modulation via Altered Chromatin Accessibility

Abstract

Metastasis and metabolic disorders contribute to most cancer deaths and are potential drug targets in cancer treatment. However, corresponding drugs inevitably induce myeloid suppression and gastrointestinal toxicity. Here, we report a nonpharmaceutical and noninvasive electromagnetic intervention technique that exhibited long-term inhibition of cancer cells. Firstly, we revealed that optical radiation at the specific wavelength of 3.6 μm (i.e., 83 THz) significantly increased binding affinity between DNA and histone via molecular dynamics simulations, providing a theoretical possibility for THz modulation- (THM-) based cancer cell intervention. Subsequent cell functional assays demonstrated that low-power 3.6 μm THz wave could successfully inhibit cancer cell migration by 50% and reduce glycolysis by 60%. Then, mRNA sequencing and assays for transposase-accessible chromatin using sequencing (ATAC-seq) indicated that low-power THM at 3.6 μm suppressed the genes associated with glycolysis and migration by reducing the chromatin accessibility of certain gene loci. Furthermore, THM at 3.6 μm on HCT-116 cancer cells reduced the liver metastasis by 60% in a metastatic xenograft mouse model by splenic injection, successfully validated the inhibition of cancer cell migration by THM in vivo. Together, this work provides a new paradigm for electromagnetic irradiation-induced epigenetic changes and represents a theoretical basis for possible innovative therapeutic applications of THM as the future of cancer treatments.