Butyrate blocks the accumulation of CDC2 mRNA in late G1 phase but inhibits both the early and late G1 progression in chemically transformed mouse fibroblasts BP-A31.
Sodium butyrate (6 mM) blocks the resumption of the cell division cycle in serum-deprived chemically transformed Balb/c-3T3 mouse fibroblasts (BP-A31). The inhibition of G1 progression by sodium butyrate is not restricted to a specific mitogenic signaling pathway and is equally effective when tetradecanoyl phorbol acetate (TPA), insulin, or fetal calf serum (FCS) is used as inducer. The inhibitor acts in early as well as late G1 phase as indicated by experiments in which inhibitor was added and withdrawn at different times after restimulation of quiescent cells by FCS. At the gene expression level, sodium butyrate does not affect the inducibility of early cell cycle-related genes (c-myc, c-jun) while blocking the induction of cdc 2 mRNA, a late G1 marker. We conclude that sodium butyrate does not interfere with the growth factor signaling pathways regulating the (early) cell cycle-related gene expression. However, the presence of sodium butyrate early in G1 phase inhibits the cascade of events leading eventually to the expression of late G1-characteristic genes such as cdc2. The antimitogenic activity of sodium butyrate may be related to its interference with an (unknown) process involved in the "mitogenic" cascade.
Charollais
R H
RH
INSERM U55, Hôpital St. Antoine, Paris, France.
Buquet
C
C
Mester
J
J
D000818:Animals; D001564:Benzo(a)pyrene; D002087:Butyrates / Q000494:pharmacology*; D020148:Butyric Acid; D016203:CDC2 Protein Kinase / Q000235:genetics*; D002455:Cell Division / Q000235:genetics; D002461:Cell Line, Transformed; D004268:DNA-Binding Proteins / Q000235:genetics; D015536:Down-Regulation; D005347:Fibroblasts / Q000166:cytology; D016193:G1 Phase / Q000187:drug effects* / Q000235:genetics; D006133:Growth Substances / Q000502:physiology; D051379:Mice; D016274:Oncogene Protein p55(v-myc) / Q000235:genetics; D011061:Poly A / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics
D002087:Butyrates; D004268:DNA-Binding Proteins; D006133:Growth Substances; D016274:Oncogene Protein p55(v-myc); D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D014157:Transcription Factors; D020148:Butyric Acid; D011061:Poly A; D001564:Benzo(a)pyrene; D016203:CDC2 Protein Kinase