Targeted Osmotic Lysis of H28 Mesothelioma Cells

Abstract

Mesothelioma is an aggressive cancer of the pleura cells of the chest cavity commonly linked to asbestos exposure. With a post‐diagnosis prognosis of between 6 and 12 months. Traditional chemotherapy increases survival time by only 11 weeks. Targeted Osmotic Lysis (TOL) is a novel cancer therapeutic that exploits cancer cells' upregulation of Voltage‐Gated Sodium Channels (VGSC) by pairing a pharmacological blocker of Na+, K+‐ATPase (sodium pumps), such as digoxin or ouabain, with electric or magnetic stimulation of VGSCs. The increase in intracellular Na+ causes an osmotic lysis of cells that over‐express VGSCs. TOL has been shown to selectively lyse highly invasive breast cancer cells, such as MDA‐MB 231, while leaving the normal tissue intact. To test the hypothesis that TOL would be an effective treatment for mesothelioma, we incubated H28 mesothelioma cells or MeT‐5A normal pleural effusion cells in 0–500 nM digoxin for 10 min, then activated the VGSCs with a 0–5 VDC electric current for 30 min. Using video microscopy, lysis was assessed by two independent observers with cytosolic extrusion as the measure. TOL effectively lysed H28 cells dose‐ and stimulus‐dependently, with a maximum cell death of 94.2% Less than 5% of cells in the Drug only, Stimulation only, and Non‐treated groups died (p<.0001). MeT‐5A cells did not lyse. Likewise, when we used a pulsed magnetic field (90 mT, 25 pps) to stimulate VGSCs, H28 cells lysed dose‐ and stimulation‐dependently, whereas control treatments and Met‐5a cells did not. Together these results are evidence that TOL causes significant cell death in mesothelioma cells compared to the normal cells. Thus, TOL may be an effective treatment for mesothelioma.Support or Funding InformationThis research was supported by a grant from Oleander Medical TechnologiesThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.