Involvement of H2O2 and O2- in the cytotoxicity of N-β-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-dihydroxyphenylaianine (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 (H2O2) 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.