Background: Hepatocellular carcinoma (HCC), a leading cause of cancer death worldwide, now has the fastest growing rate in the United States. The intrabuccal administration of amplitude modulated electromagnetic fields (AM-EMF) is a novel, minimally invasive treatment modality. There is clinical evidence that this novel treatment approach elicits therapeutic responses in patients with cancer (1, 2). However, there is no known mechanism explaining the anti-proliferative effect of very low intensity electromagnetic fields. Methods: Hepatocellular carcinoma cells were exposed to 27.12 MHz radiofrequency electromagnetic fields using in vitro exposure systems designed to replicate in vivo conditions. Cancer cells were exposed to tumor-specific modulation frequencies, previously identified by biofeedback methods in patients with a diagnosis of cancer. Control modulation frequencies consisted of randomly-chosen modulation frequencies within the same 100 Hz to 21 kHz range as cancer-specific frequencies. Growth inhibition was evaluated by measuring tritiated thymidine incorporation. RNA-Seq was used to identify genes with differential expression in cells exposed to HCC-specific AM-EMF. Confocal laser scanning microscopy allowed the visualization of the mitotic spindle. Karyotype assessment compared HepG2 receiving HCC-specific AM-EMF to those not receiving exposure. Results: The growth of hepatocellular carcinoma and breast cancer cells was significantly decreased by hepatocellular carcinoma-specific and breast cancer-specific modulation frequencies, respectively. However, the same frequencies did not affect proliferation of nonmalignant hepatocytes or breast epithelial cells. Inhibition of hepatocellular carcinoma cell proliferation was associated with downregulation of XCL2 and PLP2. Furthermore, hepatocellular carcinoma-specific modulation frequencies disrupted the mitotic spindle. Karyotype analysis was unrevealing. Conclusion: These findings uncover a novel mechanism controlling the growth of cancer cells at specific modulation frequencies without affecting normal tissues, which may have broad implications in oncology. Reference List (1) Barbault A, Costa F, Bottger B, Munden R, Bomholt F, Kuster N, et al. Amplitude-modulated electromagnetic fields for the treatment of cancer: Discovery of tumor-specific frequencies and assessment of a novel therapeutic approach. Journal of Experimental & Clinical Cancer Research 2009;28:51. (2) Costa FP, de Oliveira AC, Meirelles R, Machado MCC, Zanesco T, Surjan R, et al. Treatment of advanced hepatocellular carcinoma with very low levels of amplitude-modulated electromagnetic fields. Br J Cancer 2011;105:640-8.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 916A. doi:1538-7445.AM2012-916A