Ethanol treatment of hepatocellular carcinoma: high potentials of low concentrations.
Primary hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide, which is associated with a very poor prognosis. A curative treatment is difficult to achieve and is only possible in a low number of patients. Therefore, many different therapeutic strategies have been developed as alternative treatment. Among these, percutaneous injection of high concentrations of ethanol (>50 mM) has been proven to be effective for the treatment of small HCC (less than 3 cm in diameter). However, the principal problem with using ethanol is its toxic effects on non-tumor cells adjacent to the tumor area. The objective of this review is to juxtapose the therapeutic potential of high and low concentrations of ethanol in the treatment of HCC, based on experimental studies obtained with the human hepatocellular tumor cell line (HepG2). They have shown that high concentrations of ethanol lead to necrosis, while low concentrations induce apoptosis due to activation of Fas-receptors. Triggering of apoptosis through Fas-receptors represents a mechanism of action different from that observed with high concentrations of ethanol, thus, reducing the complications that follow the inflammatory process due to necrosis. Therefore, the use of low concentrations of ethanol could be an effective treatment for HCC.
Castaneda
Francisco
F
Max Planck Institute for Molecular Physiology, Dortmund, Germany. francisco.castaneda@mpi-dort-mund.mpg.de
Kinne
Rolf K-H
RK
D000891:Anti-Infective Agents, Local / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000627:therapeutic use*; D053222:Fas Ligand Protein; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008562:Membrane Glycoproteins / Q000378:metabolism
D000891:Anti-Infective Agents, Local; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D000431:Ethanol