[Flow cytometric analysis of the effect of THP-adriamycin on the cell cycle traverse of RPMI-8402 cells--comparison with adriamycin].
THP-adriamycin (THP) is a new derivative of adriamycin (ADM) which is reported to have a lower cardiotoxicity than ADM. In this report, the effects of THP on cell growth, cell cycle traverse and colony-forming ability of RPMI-8402 cells were investigated in comparison with ADM. The growth-inhibitory effect of THP was equal or superior to that of ADM in this system. Analysis of the DNA histogram obtained by flow cytometry showed that THP exerted its growth-inhibitory effect by blocking cells at the G2 phase. At higher concentrations, THP inhibited the traverse of cells through the S phase and further through the whole cell cycle completely. These effects were quite similar to those of ADM, which suggested a similar mechanism of action for the two drugs from the aspect of the cell cycle. A follow-up study of cells accumulated at the G2 phase and a study on colony-forming ability revealed that the G2 phase accumulation was an irreversible and fatal effect of THP, so that G2-phase accumulation could be considered as a cytocidal effect of THP, indicating the clinical usefulness of this system for evaluation of the drug effect. From these results and the low cardiotoxicity, it was suggested that THP could be a good candidate for use as an antitumor agent in clinics.
Takamoto
S
S
Ota
K
K
D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002478:Cells, Cultured; D004273:DNA, Neoplasm / Q000032:analysis*; D004317:Doxorubicin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D005434:Flow Cytometry; D006801:Humans; D007399:Interphase / Q000187:drug effects; D007938:Leukemia / Q000473:pathology*
D004273:DNA, Neoplasm; D004317:Doxorubicin; C027260:pirarubicin