Importance of Protein Denaturation to Thermochemical Ablation of Liver Tumors

Solid tumors in the liver such as hepatocellular carcinoma, often are not amenable to chemotherapy or surgical therapies. Local “ablation” methods including thermal and chemical ablation are therefore options for treatment. Hyperthermic ablation methods (RF, microwave, HIFU and laser) can potentially accomplish treatment in a single session but are considerably more costly than chemicals. It was therefore of interest to investigate if a known protein denaturant such as urea would destroy liver tumors. Further, we wished to assess whether this destruction occurs by protein denaturation mechanisms similar to hyperthermic destruction. Specifically, Lepock showed that hyperthermic cell destruction occurs for many cells when overall protein denaturation is greater than 5% (i.e. survival drops from 95% to 5% beyond this range). In this study we report on the cytotoxicity of urea on human hepatoma HuH-7. We then quantify the amount of cellular protein denaturation associated with cytotoxicity and show that protein denaturation in excess of 5% of total protein must occur in order for significant cell killing.