Toxicity of menadione in the differentiating human colon carcinoma cell line Caco-2

The human colon adenocarcinoma cell line Caco-2 is susceptible to spontaneous enterocytic differentiation after reaching confluence and was used on day 7, 14 and 21 of culture to investigate the toxicity of the quinone menadione. Menadione was less toxic in day 7 cells compared with the older cell cultures. Enzymatic activation of menadione and glucose-6-phosphate dehydrogenase activity did not alter during differentiation. Based on these observations it was concluded that redoxcycling of menadione occurred at similar levels throughout differentiation. Further, day 7 cells proved to be more vulnerable for ATP depletion but had significantly higher levels of intracellular reduced glutathione than older cells. We conclude that these levels of cellular reduced GSH play a major role in the protection of crypt-like enterocytic cells.