Down-regulation of protein kinase CKII activity by sodium butyrate.
Butyrate, a dietary fiber derivative, is a well-known differentiating agent in cultured cell lines. In addition, its antineoplastic activity toward colon-rectum cancers has been documented both in vivo and in vitro. Despite the large amount of information on the potential clinical efficacy of butyrate, its mechanism of action at the molecular level has only been partially investigated. Here, we show that serine/threonine protein kinase CKII is a target of butyrate activity. In the human adenocarcinoma cell line, HT29, treated with 2 mM sodium butyrate, CKII activity decreases 50% at 24 and 48 hours after drug addition. The enzyme down-regulation is not due to changes in protein amount since the levels of the different CKII subunits remain constant during butyrate treatment. The data reported provide the first evidence that CKII down-regulation is involved in the signal transduction pathway started by butyrate.
Russo
G L
GL
I.S.A. Institute of Food Science and Technology, National Research Council, Avellino, Italy. glrusso@alpha.szn.it
Della Pietra
V
V
Mercurio
C
C
Della Ragione
F
F
Marshak
D R
DR
Oliva
A
A
Zappia
V
V
D000230:Adenocarcinoma / Q000201:enzymology; D000595:Amino Acid Sequence; D002087:Butyrates / Q000494:pharmacology*; D020148:Butyric Acid; D047390:Casein Kinase II; D002454:Cell Differentiation / Q000187:drug effects; D003110:Colonic Neoplasms / Q000201:enzymology; D015536:Down-Regulation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D009842:Oligopeptides / Q000737:chemistry; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013379:Substrate Specificity; D014407:Tumor Cells, Cultured
D002087:Butyrates; D004791:Enzyme Inhibitors; D009842:Oligopeptides; D020148:Butyric Acid; D047390:Casein Kinase II; D017346:Protein Serine-Threonine Kinases