Cancer cells show an up-regulation of glycolysis, they readily take up
vitamin C, and they appear more susceptible to an oxidative stress than the surrounding normal cells. Here we compare, analyse and discuss these particular hallmarks by performing experiments in murine
hepatomas (TLT cells) and freshly isolated mouse hepatocytes. The results show that rates of
lactate formation are higher in TLT cells as compared to mouse hepatocytes, but their
ATP content represents less than 25% of that in normal cells. The uptake of
vitamin C is more important in
hepatoma cells as compared to normal hepatocytes. This uptake mainly occurs through GLUT1 transporters.
Hepatoma cells have less than 10% of
antioxidant enzyme activities as compared to normal hepatocytes. This decrease includes not only the major
antioxidant enzymes, namely
catalase,
superoxide dismutase and
glutathione peroxidase, but also the GSH content. Moreover,
catalase is almost not expressed in
hepatoma cells as shown by western blot analysis. We explored therefore a selective exposure of
cancer cells to an oxidative stress induced by
pro-oxidant mixtures containing pharmacological doses of
vitamin C and a redox active compound such as
menadione (
vitamin K(3)). Indeed, the combination of
vitamin C (which accumulates in
hepatoma cells) and a
quinone undergoing a redox cycling (
vitamin K(3)) leads to an oxidative stress that kills
cancer cells in a selective manner. This differential sensitivity between
cancer cells and normal cells may have important clinical applications, as it has been observed with other
pro-oxidants like
Arsenic trioxide,
isothiocyanates,
Adaphostin.