Journal Article

Activation of protein kinase C augments butyrate-induced differentiation and turnover in human colonic epithelial cells <i>in vitro</i>

Kurt L. Rickard, Peter R. Gibson, Graeme P. Young and Wayne A. Phillips

in Carcinogenesis

Volume 20, issue 6, pages 977-984
Published in print June 1999 | ISSN: 0143-3334
Published online June 1999 | e-ISSN: 1460-2180 | DOI: https://dx.doi.org/10.1093/carcin/20.6.977
Activation of protein kinase C augments butyrate-induced differentiation and turnover in human colonic epithelial cells in vitro

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As the colonic epithelium is physiologically exposed to butyrate and to activators of protein kinase C, we examined the effect of the protein kinase C signalling pathway on butyrate-induced expression of markers of differentiation. Activators and inhibitors of protein kinase C were used in combination with butyrate and effects on the expression of markers of differentiation examined in colon cancer cell lines. When the protein kinase C activator phorbol myristate acetate (100 nM) was added for 24 h prior to the addition of 2 mM butyrate, there was a synergistic increase in alkaline phosphatase activity (154 ± 11% above that for butyrate alone, P = 0.003) in a concentration- and time-dependent manner. Butyrate-induced expression of carcinoembryonic antigen and interleukin-8, dome formation and cell turnover were also markedly augmented by pre-treatment with phorbol myristate acetate. A similar effect was observed with propionate or acetate (but not other differentiating agents), when phorbol myristate acetate and butyrate were added concurrently, or when other protein kinase C activators were used. Pharmacological inhibition of protein kinase C activity did not alter butyrate-induced alkaline phosphatase activity, but abrogated the augmentation induced by phorbol myristate acetate. We conclude that protein kinase C does not mediate the differentiating effects of butyrate on colon cancer cells, but its activation regulates butyrate-induced cellular differentiation.

Keywords: DiC8, 1,2-dioctanoyl-sn-glycerol; IL-8, interleukin-8; PdBt, phorbol 12,13-dibutyrate; PKC, protein kinase C; PMA, phorbol-12-myristate-13-acetate; OAG, 1-oleoyl-2-acetyl-rac-glycerol; SCFA, short chain fatty acids.

Journal Article.  6423 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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