Program Information
Digoxin Mediated Electromagnetically Induced Targeted Osmotic Lysis in Cancer Cells
P Maggi*, K Matthews , R Subramanian , W. T. Monroe , Louisiana State University, Baton Rouge, LA
Presentations
SU-I-GPD-T-635 (Sunday, July 30, 2017) 3:00 PM - 6:00 PM Room: Exhibit Hall
Purpose: To determine the appropriate electromagnetic stimulus parameters to induce digoxin mediated targeted osmotic lysis (TOL) of cancerous cells, while sparing healthy cells. TOL is the rupturing of cells due to uncontrolled influx of water. We investigated efficacy of electrical contact stimulus both in vitro and in vivo. We investigated magnetic non-contact stimulation in vitro.
Methods: MDA-MB-231 and MCF-12A cells were cultured, treated with digoxin, then electrically stimulated with varying waveforms, frequencies, and applied voltages. Once we identified suitable stimulus parameters to produce differential lysis, we moved to testing an in vivo murine model, where 4T1 breast cancer cells were grown into tumors on the rear flank. We compared different digoxin injection routes and timings and stimulated transdermally with a 66Hz square wave at 10Vpp. Tumor sizes were matched between the control and treatment group. In vivo TOL was quantified by necrosis percentage in stained tumor sections. We performed magnetic non-contact studies using cultured cells in a coil.
Results: Targeted osmotic lysis exhibited itself in culture as a swelling and bursting of the MDA cells, but not the MCF cells. This differential effect was observed most strongly with a 3Vpp square wave centered about 1.5V, 66Hz, 66% duty cycle. For the murine model, multiple intraperitoneal injections provided the most consistent administration of digoxin and the treatment achieved a 29% increase in tumor necrosis percentage (67% +- 18% treatment vs 38% +- 29% control), p<0.01. The tumor sizes did not violate the null hypothesis, p=0.11. For non-contact studies, a low frequency ramped magnetic field produced the most TOL, although the damage was not as catastrophic as the contact studies.
Conclusion: Differential targeted osmotic lysis in cancerous cells by direct electrical stimulation is achievable both in vitro and in vivo. Current non-contact magnetic stimulus tests are encouraging, but additional study is needed.
Funding Support, Disclosures, and Conflict of Interest: Supported in part by: Louisiana Board of Regents Support Fund, LEQSF(2015-17)-RD-B-02, and in part by a contract from Oleander Medical Technologies.
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