Effects of cycloheximide on B-chronic lymphocytic leukaemic and normal lymphocytes in vitro: induction of apoptosis.
A number of reports indicate that protein synthesis is a requirement for the occurrence of apoptosis. In this study, the effect of the protein synthesis inhibitor cycloheximide (CHM) on spontaneous apoptosis of B-chronic lymphocytic leukaemia (B-CLL) cells, previously shown to occur when they are cultured in RPMI-1640 medium with autologous or heterologous serum, was examined. No definite inhibition of apoptosis was observed. Indeed, CHM-treatment augmented apoptosis in the B-CLL cultures and also induced apoptosis of cultured normal peripheral blood lymphocytes. Augmentation was dose-dependent for B-CLL cells over the concentration range 10(-6) M (0.28 micrograms ml-1) to 10(-2) M (2800 micrograms ml-1), resulting in 9% to 98% apoptosis respectively by 24 h of culture (r = 0.619, P = 0.0008). Normal lymphocytes were affected by CHM over the range 10(-4) M to 10(-2) M, resulting in 7% to 74% apoptosis respectively (r = 0.794, P = 0.0001). Inhibition of protein synthesis in these cells by CHM was virtually complete at a concentration of 10(-3) M. The findings are in accord with some recent reports indicating that suppression of protein synthesis by CHM does not inhibit apoptosis in all circumstances. They also illustrate the marked susceptibility of B-CLL cells, compared with normal lymphocytes, to the induction of apoptosis by this drug. The manner in which CHM triggers apoptosis of some cell types is at present uncertain.
Collins
R J
RJ
Department of Pathology, Royal Brisbane Hospital, Herston, Queensland, Australia.
Harmon
B V
BV
Souvlis
T
T
Pope
J H
JH
Kerr
J F
JF
D015703:Antigens, CD / Q000032:analysis; D001798:Blood Proteins / Q000096:biosynthesis / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology*; D004247:DNA / Q000097:blood / Q000302:isolation & purification; D004273:DNA, Neoplasm / Q000302:isolation & purification; D006801:Humans; D016130:Immunophenotyping; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000276:immunology / Q000473:pathology*; D008214:Lymphocytes / Q000166:cytology* / Q000187:drug effects / Q000276:immunology; D008715:Methionine / Q000097:blood; D012016:Reference Values
D015703:Antigens, CD; D001798:Blood Proteins; D004273:DNA, Neoplasm; D004247:DNA; D003513:Cycloheximide; D008715:Methionine