Potentiation of doxorubicin cytotoxicity by (+)-1,2-bis-(3,5-dioxopiperazinyl-1-yl) propane (ICRF-187) in human leukemic HL-60 cells.
The bisdioxopiperazine propane, ICRF-187, has been reported to potentiate doxorubicin cytotoxicity in certain tumor cell lines; however, the mechanism of this interaction is not known. In order to define the mechanism of this interaction, we examined the effects of ICRF-187 on doxorubicin cytotoxicity, free radical formation, and drug accumulation in human leukemia HL-60 cells. Studies show that ICRF-187 synergistically potentiated doxorubicin cytotoxicity in HL-60 cells. This potentiation of doxorubicin cytotoxicity by ICRF-187 appeared to result from enhanced drug dependent free radical formation without effecting doxorubicin uptake in HL-60 cells.
Monti
E
E
Biochemical Pharmacology Section, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
Sinha
B K
BK
D001692:Biological Transport / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003630:Daunorubicin / Q000378:metabolism; D004317:Doxorubicin / Q000494:pharmacology*; D004357:Drug Synergism; D004578:Electron Spin Resonance Spectroscopy; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute; D010879:Piperazines / Q000494:pharmacology*; D011929:Razoxane / Q000494:pharmacology*; D013237:Stereoisomerism; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000187:drug effects*
D010879:Piperazines; D011929:Razoxane; D004317:Doxorubicin; D003630:Daunorubicin