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J. Biochem, 2004, Vol. 135, No. 4 465-469
© 2004 The Japanese Biochemical Society

MOLECULAR BIOLOGY

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

Takeshi Nishikawa, Satoshi Nishikawa, Nobuko Akiyama and Shunji Natori*

Natori Special Laboratory, The Institute of Physical and Chemical Research (RIKEN), 2-1 Hirosawa, Wako, Saitama 351-0198

N-ß-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-435S 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 T47D 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-435S 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.

* To whom correspondence should be addressed. Tel: +81-48-467-9437, Fax: +81-48-462-4693, E-mail: natori{at}postman.riken.go.jp.


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