Arrest in late G2 or prophase of cell cycle induced by 4,4-(1,2-ethanediyl) bis (1-isobutoxycarbonyloxymethyl 2, 6-piperazinedione) (MST-16) in cultured L1210 cells.
The effects of MST-16, a new antitumor agent derived from bis (2, 6-dioxopiperazine), on cell growth, cell-cycle progression and DNA synthesis, alone and in combination with other antitumor agents, were investigated in murine leukemia L1210 cells in vitro. The drug showed dose-dependent inhibition of cell growth, and this effect was cell-cycle phase-specific. Flow cytometric analysis indicated that the drug could retard-arrest the cells in late G2 phase or prophase and that it did not affect the progression from G1 to G2 phase. In the presence of MST-16, the change in 3H-thymidine incorporation was proportional to the retardation-arrest of the cells, suggesting that MST-16 has no direct action on DNA synthesis itself. MST-16 could continuously retard the cells which were arrested by etoposide (VP-16); and vincristine (VCR) could block the progression of the cells arrested by MST-16, but not vice versa. The addition of MST-16 followed by VCR was more effective than simultaneous addition of the 2 drugs on inhibition of cell growth. These results will be useful in designing a reasonable regimen of MST-16 chemotherapy for malignancies.
Liu
Y P
YP
First Department of Internal Medicine, Fukui Medical School, Japan.
Araya
S
S
Nakamura
T
T
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D004247:DNA / Q000096:biosynthesis; D004347:Drug Interactions; D005047:Etoposide / Q000494:pharmacology; D005434:Flow Cytometry; D016195:G2 Phase / Q000187:drug effects*; D007939:Leukemia L1210 / Q000473:pathology*; D051379:Mice; D010879:Piperazines / Q000008:administration & dosage / Q000494:pharmacology*; D011418:Prophase / Q000187:drug effects*; D014407:Tumor Cells, Cultured; D014750:Vincristine / Q000008:administration & dosage / Q000494:pharmacology
D000970:Antineoplastic Agents; D010879:Piperazines; D014750:Vincristine; D005047:Etoposide; D004247:DNA; C057773:sobuzoxane