Involvement of H2O2 and O2- in the cytotoxicity of N-beta-alanyl-5-S-glutathionyl-3,4-dihydroxyphenylalanine (5-S-GAD), a novel insect-derived anti-tumor compound.
We investigated the mechanism underlying the cytotoxicity of N-beta-alanyl-5-S-glutathionyl-3,4-dihydroxyphenylalanine (5-S-GAD) toward MDA-MB-435S, a human breast cancer cell line sensitive to 5-S-GAD. We found that the addition of either catalase or superoxide dismutase (SOD) to a culture medium of MDA-MB-435S cells almost completely abolished the cytotoxic effect of 5-S-GAD, indicating that both hydrogen peroxide (H(2)O(2)) and the superoxide anion (O(2)(-)) are involved in the cytotoxic action of 5-S-GAD. We compared the catalase and SOD levels in MDA-MB-435S and T47D, a cell line resistant to 5-S-GAD, and found that the levels in resistant cells are higher than those in sensitive cells. We concluded that the levels of these enzymes are crucial determinants of the sensitivity or insensitivity of cells to 5-S-GAD.
Akiyama
Nobuko
N
Natori Laboratory, The Institute of Physical and Chemical Research (RIKEN), Wako, Saitama 351-0198, Japan.
Natori
Shunji
S
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002374:Catalase / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D004295:Dihydroxyphenylalanine / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D004175:Diptera / Q000737:chemistry; D019008:Drug Resistance, Neoplasm; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D005260:Female; D005978:Glutathione / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D013482:Superoxide Dismutase / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism*; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000201:enzymology
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; C100496:N-beta-alanyl-5-S-glutathionyl-3,4-dihydroxyphenylalanine; D013481:Superoxides; D004295:Dihydroxyphenylalanine; D006861:Hydrogen Peroxide; D002374:Catalase; D013482:Superoxide Dismutase; D011505:Protein-Tyrosine Kinases; D005978:Glutathione