S. Furusawa et al., INHIBITION OF DOXORUBICIN-INDUCED CELL-DEATH IN-VITRO AND IN-VIVO BY CYCLOHEXIMIDE, Biological & pharmaceutical bulletin, 18(10), 1995, pp. 1367-1372
We studied the effects of the protein synthesis inhibitor, cycloheximi
de (CH), on cell killing by doxorubicin (DOX) in vitro and ill vivo. A
t the concentration of CH used (1 mu g/ml) the cytotoxicity of DOX was
reduced in cultured P388 leukemia cells. An analysis of the DNA histo
gram obtained by flow cytometry showed that DOX exerts its growth-inhi
bitory effect by blocking the cell cycle at the G(2)/M phase in P388 c
ells. Treatment with CH diminished this blocking effect. When CH was a
dded to the growth medium before DOX exposure, no change in intracellu
lar DOX accumulation was observed. Treatment with CH (15 mg/kg) signif
icantly diminished the lethality of DOX (20mg/kg) in mice and it also
reduced the antitumor activity of mice with P388 leukemia. Thus, CH in
hibited cell death induced by DOX in vitro and in vivo. These results
suggest that CH has an antagonistic effect on the pharmacological acti
ons of DOX in cells and mice. The cytoprotective effect of CH may be d
ue to protein synthesis inhibition.