Correlation between the Catalase Level in Tumor Cells and Their Sensitivity to <i>N</i>-β-Alanyl-5-<i>S</i>-Glutathionyl-3, 4-Dihydroxyphenylalanine (5-S-GAD)

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  • Nishikawa Takeshi
    Natori Special Laboratory, The Institute of Physical and Chemical Research (RIKEN)
  • Nishikawa Satoshi
    Natori Special Laboratory, The Institute of Physical and Chemical Research (RIKEN)
  • Akiyama Nobuko
    Natori Special Laboratory, The Institute of Physical and Chemical Research (RIKEN)
  • Natori Shunji
    Natori Special Laboratory, The Institute of Physical and Chemical Research (RIKEN)

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  • Correlation between the Catalase Level in Tumor Cells and Their Sensitivity to N-β-Alanyl-5-S-Glutathionyl-3,4-Dihydroxyphenylalanine(5-S-GAD)
  • Correlation between the Catalase Level in Tumor Cells and Their Sensitivity to N ベータ Alanyl 5 S Glutathionyl 3 4 Dihydroxyphenylalanine 5 S GAD
  • Correlation between the Catalase Level in Tumor Cells and Their Sensitivity to N- -Alanyl-5-S-Glutathionyl-3,4-Dihydroxyphenylalanine (5-S-GAD)

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Abstract

N-β-Alanyl-5-S-glutathionyl-3, 4-dihydroxyphenylalanine (5-S-GAD) exhibits selective cytotoxicity toward certain human tumor cell lines. 5-S-GAD has been shown to release hydrogen peroxide autonomously. Hydrogen peroxide is converted to water and oxygen by catalase. The purpose of this study is to determine whether or not 5-S-GAD exhibits selective cytotoxicity toward tumor cells with low catalase levels, but not toward ones with high catalase levels. We transfected MDA-MB-435 S cells, which are sensitive to 5-S-GAD, with catalase cDNA to establish high catalase producer cells, and then examined their 5-S-GAD sensitivity. Similarly, we repressed catalase expression in T47 D cells, which are insensitive to 5-S-GAD, by catalase RNA interference to create low catalase producer cells, and then examined their 5-S-GAD sensitivity. We show that the overexpression of catalase made MDA-MB-435 S cells insensitive to 5-S-GAD, whereas the suppression of catalase made T47D cells sensitive to 5-S-GAD. The cellular catalase level was found to be crucial for cell sensitivity to 5-S-GAD.

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