Abstract 5612: Cancer cell proliferation is inhibited by specific modulation frequencies.

Abstract

Abstract Purpose: Hepatocellular carcinoma (HCC) incidence in the US is dramatically increasing. Five-year survival remains 3-5%, demonstrating urgent need for additional therapies. Intrabuccal administration of amplitude modulated electromagnetic fields (RF EMF) is a novel, minimally invasive treatment modality which results in whole body absorption of very low levels of RF EMF. Clinical studies show that this treatment approach elicits therapeutic responses in patients with hepatocellular carcinoma and breast cancer. Using an in vitro exposure system replicating the levels of exposure achieved in humans, we have described a phenotype in HCC cells following RF EMF exposure that included proliferative inhibition, modulation of gene expression, and disruption of the mitotic spindle. This phenotype was specific for HCC cells exposed to HCC-specific RF EMF at exposure levels ranging from 0.03 to 0.4 W/kg. Methods: HCC cells were exposed to 27.12 MHz electromagnetic fields modulated at specific frequencies from 400 Hz to 21 kHz, previously identified in HCC patients. MicroRNA arrays compared exposed and control groups of HCC cells, with microRNA validation followed by Western blot of target genes and proteins. HCC xenografts were injected subcutaneously in NOD SCID mice. Following palpable tumor establishment, mice were exposed to HCC-specific RF EMF at a specific absorption rate of 0.4 W/kg, euthanized following excessive tumor burden, and evaluated by immunohistochemistry. Results: We identified increased levels of miRNAs targeting proteins belonging to the PI3K pathway, specifically IP3/DAG signaling and intracellular calcium release. This pathway is frequently disrupted in HCC and breast cancer, making it an excellent candidate for modulation by RF EMF; furthermore, downstream effects include: cell cycle progression, proliferation, inhibition of apoptosis, and cell migration. We observed tumor shrinkage in mice exposed to HCC-specific modulation frequencies and residual xenograft tumor cells were infiltrated with fibrous tissue and showed significantly decreased proliferation and increased apoptosis. There was no evidence of altered cell proliferation or fibrosis in other organs. Conclusion: These findings are the first evidence of the efficacy and safety of RF EMF in HCC using a subcutaneous xenograft model and uncover a novel mechanism that controls cancer cell growth in vivo at specific modulation frequencies, possibly through modulation of PI3K signaling and downstream release of intracellular calcium. Citation Format: Hugo Jimenez, Jacquelyn W. Zimmerman, Michael J. Pennison, Ivan Brezovich, Nengjun Yi, Celeste T. Yang, Ryne Ramaker, Devin Absher, Richard M. Myers, Niels Kuster, Frederico P. Costa, Alexandre Barbault, Boris Pasche. Cancer cell proliferation is inhibited by specific modulation frequencies. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5612. doi:10.1158/1538-7445.AM2013-5612 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.