Quinone Thiol Amino acid ESR Semiquinone anion radical

The mechanisms of toxicity to isolated rat hepatocytes of two structurally related naphthoquinones have been studied. Both 5-OH-1,4-naphthoquinone (5-OH-1,4-NQ; juglone) and 2-OH-1,4-naphthoquinone (2-OH-1,4-NQ; lawsone) caused a concentration-dependent cytotoxicity to hepatocytes which was preceded by a depletion of intracellular glutathione. 5-OH-1,4-NQ caused a depletion of intracellular glutathione when incubated either at 4 degrees C or 37 degrees C whereas 2-OH-1,4-NQ caused a depletion of intracellular glutathione when the hepatocytes were incubated at 37 degrees C but not at 4 degrees C. 5-OH-1,4-NQ but not 2-OH-1,4-NQ reacted with glutathione in buffered solution. These results suggested that the depletion of intracellular glutathione by 2-OH-1,4-NQ is enzyme mediated whereas in the case of 5-OH-1,4-NQ the direct chemical reaction with gluathione may be largely responsible for the depletion. A critical role for depletion of protein thiols in menadione-induced cytotoxicity has been proposed. In agreement with earlier work, menadione caused a decrease in protein sulphydryls prior to cell death, however, at cytotoxic concentrations of both 2-OH-1,4-NQ and 5-OH-1,4-NQ this decrease only accompanied rather than preceeded cell death. The mechanism of toxicity of 5-OH-1,4-NQ is similar to that of other naphthoquinones and involves formation of its corresponding naphthosemiquinone, active oxygen species and redox cycling as it stimulated a disproportionate increase in both microsomal NADPH oxidation and oxygen consumption.(ABSTRACT TRUNCATED AT 250 WORDS)

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Summary 1-Naphthol was selectively toxic to human colorectal tumours compared to corresponding normal colonic tissue removed at surgery and maintained in short-term organ culture. Nineteen of 24 tumours studied have shown a significant differential response. Three human colonic adenocarcinoma xenografts, in the shortterm organ culture system, displayed the same response to l-naphthol as primary tumours removed at surgery. I-Naphthol, 1,2-and 1,4-naphthoquinone were also toxic to two human colonic adenocarcinoma cell lines, LoVo and COLO 206. The selective toxicity of l-naphthol is mediated in part through an accumulation of l-naphthol in the tumour tissue due to impaired conjugation by the tumour. The higher concentrations of 1-naphthol may then exert their toxicity either directly or by formation of naphthoquinones. Some indirect evidence was obtained for the possible involvement of 1,2-or 1,4-naphthoquinone in the cytotoxicity of 1-naphthol. Our studies suggest that further studies are warranted of the possible use of l-naphthol or related compounds as antitumour agents.