Spectroscopic and calorimetric evaluation of chemically induced protein denaturation in HuH-7 liver cancer cells and impact on cell survival

Rajagopal N. Aravalli, Jeunghwan Choi, Shoji Mori, Dushyant Mehra, Jinping Dong, John C. Bischof, Erik N.K. Cressman

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Solid tumors such as hepatocellular carcinoma are very often not amenable to chemotherapy and radiotherapy. Local ablation methods, including chemical ablation with absolute ethanol, are therefore an option for treatment but lack of information about the mechanism of devitalization leading to cell death is a hindrance to further adoption. Systemic toxicity also has limited the amount of ethanol that can be used in a single treatment session. Therefore we evaluated the mechanism of urea, a denaturant with little or no systemic toxicity, for potential use in chemical ablation. In this study we report on the use of three methods to analyze the effects in cell culture with a view towards eventual clinical application. Human hepatoma HuH-7 cells were analyzed at several time points after treatment using FTIR, DSC, and Raman microspectroscopy based on MTT and PI-exclusion viability assays. Time course fractional denaturation data plotted against viability show that a 50% viability drop occurs after only a 10-20% drop in overall protein denaturation. Other methods of cell death such as apoptosis may also be operative, but this result implies that protein denaturation is one of the major mechanisms of cell death. This is in line with what has been previously suggested for purely thermal methods, and opens the way to mechanism-based improvements in chemical ablation of solid tumors.

元の言語英語
ページ(範囲)467-473
ページ数7
ジャーナルTechnology in Cancer Research and Treatment
11
発行部数5
DOI
出版物ステータス出版済み - 10 2012
外部発表Yes

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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