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TOXICOLOGY

In Vitro Cytotoxicity of 4-Methylcatechol in Murine Tumor Cells: Induction of Apoptotic Cell Death by Extracellular Pro-Oxidant Action

Departments of Pharmacology (K.M.) and Molecular Bacteriology (H.A., Y.O.), School of Medicine, The University of Tokushima, Kuramoto, Tokushima, Japan

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.

Address correspondence to: Dr. Kyoji Morita, Department of Pharmacology, Tokushima University School of Medicine, 3-18-15 Kuramoto, Tokushima 770-8503, Japan. E-mail: km{at}basic.med.tokushima-u.ac.jp

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