Sodium butyrate inhibits c-myc splicing and interferes with signal transduction in ovarian carcinoma cells.
Sodium butyrate (NaB), a physiologically produced short chain fatty acid, dramatically changes the growth rate and also the morphology of a fast growing subclone (N.1) derived from the heterogenous human ovarian carcinoma HOC-7. The mRNA of the growth related proto-oncogene c-myc, constitutively expressed in N.1 cells decreased significantly within 24 h of NaB treatment and remained suppressed until the NaB block was released. Down-regulation was accomplished partially by accelerating degradation of c-myc mRNA and by inhibiting splicing of c-myc transcripts. We demonstrated that NaB blocked general mechanisms in signal transduction, such as the release of Ca2+ from intracellular stores, and modulated the activity of serine/threonine kinases. The multiple effects of sodium butyrate on HOC-7 derivatives, as well as on a variety of other cell types investigated by others, may be due to interference with general mechanisms of signal transduction.
Krupitza
G
G
Ludwig Boltzmann Institute of Applied Cancer Research, 3rd Medical Department-Oncology, Kaiser Franz Josef-Hospital, Austria.
Harant
H
H
Dittrich
E
E
Szekeres
T
T
Huber
H
H
Dittrich
C
C
D000230:Adenocarcinoma; D001483:Base Sequence; D015152:Blotting, Northern; D002087:Butyrates / Q000494:pharmacology*; D020148:Butyric Acid; D002460:Cell Line; D002467:Cell Nucleus / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D003001:Cloning, Molecular; D017931:DNA Primers; D005260:Female; D016259:Genes, myc / Q000187:drug effects*; D006801:Humans; D007438:Introns; D008969:Molecular Sequence Data; D010051:Ovarian Neoplasms; D016133:Polymerase Chain Reaction; D000090063:Proto-Oncogene Mas; D012326:RNA Splicing / Q000187:drug effects*; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D014158:Transcription, Genetic / Q000187:drug effects; D014407:Tumor Cells, Cultured
D002087:Butyrates; D017931:DNA Primers; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D012333:RNA, Messenger; D020148:Butyric Acid