Cytostatic effect of deoxyspergualin on a murine leukemia cell line L1210.
The mode of antiproliferative action of deoxyspergualin (NKT-01) was examined. The growth-inhibitory effect on a murine leukemia cell line L1210 following treatment with NKT-01 was time-dependent, and there was little or no effect on the syntheses of DNA and RNA. Thus, the inhibitory activity of NKT-01 was not attributable to the inhibition of DNA and RNA syntheses. The influence of NKT-01 on cell cycle progression was studied by flow cytometric analysis. Bromodeoxyuridine/DNA distribution patterns in cells that were treated for 72 h, showed that the growth inhibition is due to the delay of cell cycle progression but not to cytotoxicity. This finding was also supported by evidence that the treated cells were re-proliferative in fresh medium. In addition, a majority of drug-treated cells was prevented from traversing from the G0/G1 phase to the S phase by 144 h or longer exposure to NKT-01. The results suggest that NKT-01 is cytostatic, preventing G0/G1-S progression.
Hiratsuka
M
M
Research Laboratories, Pharmaceuticals Group, Nippon Kayaku Co., Ltd., Tokyo.
Kuramochi
H
H
Takahashi
K
K
Takeuchi
T
T
Oshimura
M
M
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects*; D004273:DNA, Neoplasm / Q000096:biosynthesis; D006146:Guanidines / Q000494:pharmacology*; D007939:Leukemia L1210; D051379:Mice; D012334:RNA, Neoplasm / Q000096:biosynthesis
D000903:Antibiotics, Antineoplastic; D004273:DNA, Neoplasm; D006146:Guanidines; D012334:RNA, Neoplasm; C037258:gusperimus