Correlation between the catalase level in tumor cells and their sensitivity to N-beta-alanyl-5-S-glutathionyl-3,4-dihydroxyphenylalanine (5-S-GAD).
N-beta-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.
Nishikawa
Takeshi
T
Natori Special Laboratory, The Institute of Physical and Chemical Research (RIKEN), 2-1 Hirosawa, Wako, Saitama 351-0198.
Nishikawa
Satoshi
S
Akiyama
Nobuko
N
Natori
Shunji
S
D001483:Base Sequence; D015153:Blotting, Western; D002374:Catalase / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004295:Dihydroxyphenylalanine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005822:Genetic Vectors / Q000235:genetics; D005978:Glutathione / Q000031:analogs & derivatives* / Q000494:pharmacology*; D006801:Humans; D034622:RNA Interference / Q000502:physiology; D034741:RNA, Small Interfering / Q000235:genetics; D014162:Transfection
C100496:N-beta-alanyl-5-S-glutathionyl-3,4-dihydroxyphenylalanine; D034741:RNA, Small Interfering; D004295:Dihydroxyphenylalanine; D002374:Catalase; D005978:Glutathione