Assessment of the in vitro cytotoxicity has recently been become popular as a primary screening method for evaluating the antitumor activities of various chemicals and natural substances. For example,
quercetin and related phenolic compounds, present in teas, wines, and other plant products, have been shown to cause their cytotoxic effects on
tumor cells in culture, proposing their protective effects against the development of
cancer. However,
4-methylcatechol, a metabolite produced in the intestinal tract after ingestion, has been shown to cause the promotion rather than suppression of
tumor in rat stomach despite its in vitro cytotoxic activity. To address the inconsistency between its in vivo and in vitro actions, the effect of
4-methylcatechol on the viabilities of murine
tumor cells was examined, and
4-methylcatechol was shown to reduce their viabilities through the induction of apoptosis. In addition, since
catechol compounds have been shown to have a
complex mixture of
pro-oxidant and
antioxidant actions in the in vitro assay systems, the cytotoxic activity of
4-methylcatechol was reassessed in the presence of either
catalase or reduced-form
glutathione, and both of them were shown to protect the cells against the damage induced by
4-methylcatechol. Moreover, the generation of
hydrogen peroxide was observed by incubating the
drug in the growth medium with or without the cells. These findings indicate that, similar to other
catechol compounds,
4-methylcatechol may induce the apoptotic death of murine
tumor cells through its extracellular
pro-oxidant action on the cells.