Suppression of the development of murine myeloid leukemia with granulocyte colony-stimulating factor by inducing apoptosis of leukemic cells.
We studied the antileukemic effect of recombinant human granulocyte colony-stimulating factor (rhG-CSF) by using a radiation-induced murine myeloid leukemia cell line C2M-A5. Intravenous inoculation of C2M-A5 cells into C3H/He mice resulted in the development of myeloid leukemia. However, the leukemic death of the mice was completely suppressed by the subcutaneous injections of rhG-CSF. In order to clarify the mechanism of the suppression, effects of rhG-CSF on C2M-A5 cells were studied in vitro. While C2M-A5 cells grew exponentially in the absence of rhG-CSF, the viability, the growth, and the self-renewal capacity of C2M-A5 cells were all suppressed in cultures in the presence of rhG-CSF. Preincubation with rhG-CSF for 48 h deprived C2M-A5 cells of the ability to induce leukemia in syngeneic mice. Morphological examination revealed the appearance of apoptotic changes of C2M-A5 cells in cultures containing rhG-CSF over the 2-day incubation period. In gel electrophoresis, the DNA from C2M-A5 cells incubated with rhG-CSF for 48 h showed a ladder of degradated DNA bands compatible with apoptosis. From these results, we concluded that the apoptosis of C2M-A5 cells played a key role in the antileukemic effect of rhG-CSF.
Bessho
M
M
First Department of Internal Medicine, Saitama Medical School, Iruma-gun, Japan.
Yoshida
S
S
Sakate
K
K
Murohashi
I
I
Jinnai
I
I
Hirashima
K
K
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D016466:CHO Cells / Q000166:cytology / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D006224:Cricetinae; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use*; D007279:Injections, Subcutaneous; D007951:Leukemia, Myeloid / Q000188:drug therapy* / Q000473:pathology / Q000517:prevention & control; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D009368:Neoplasm Transplantation; D014407:Tumor Cells, Cultured / Q000187:drug effects
D016179:Granulocyte Colony-Stimulating Factor