title: Butyrate metabolism in human colon carcinoma cells: implications concerning its growth-inhibitory effect.
abstract: Butyrate and acetate are bacterial metabolites present in the large intestine lumen. Although butyrate is well known to inhibit the in vitro proliferation of human colon carcinoma cells in a process involving the hyperacetylation of specific nuclear histones, little is known about the possible link between butyrate metabolism and its growth-inhibitory effect. In a previous study (Leschelle et al., 2000, Eur J Biochem 267: 6435-6442), we showed that butyrate accumulates and is metabolized in HT-29 Glc(-/+) cells without increasing oxygen consumption. In the present study, using the same cell line incubated with (14)C-labeled butyrate, we determined that a minor part of (14)C from butyrate was recovered in nuclear histones. Unlike butyrate, acetate exerted no effect on cell growth but was a precursor for overall net histone acetylation. Although butyrate was able to increase the cellular AMP/ADP ratio, it did not affect the ATP cell content or the adenylate charge or the oxidation of endogenous L-glutamine. Butyrate oxidation was found to be markedly sensitive to the presence of other substrates with D-glucose decreasing this oxidation and L-malate stimulating it. Furthermore, in the presence of L-malate, the growth-inhibitory effect of butyrate was significantly weaker than in its absence. From these data, we conclude that the metabolism of butyrate downstream acetyl-CoA synthesis is not involved in the butyrate antiproliferative effect. The suggestion that butyrate metabolism in mitochondria is not used in these cells as a fuel but acts as a regulator of butyrate free concentrations (thus limiting its action upon cellular targets), is discussed.
authors.affiliation: INRA, CNRH-IdF, UMR 914 Nutrition Physiology and Ingestive Behavior, Paris, France.
authors.forename: Mireille
authors.initials: M
authors.lastname: Andriamihaja
authors.forename: Catherine
authors.initials: C
authors.lastname: Chaumontet
authors.forename: Daniel
authors.initials: D
authors.lastname: Tome
authors.forename: François
authors.initials: F
authors.lastname: Blachier