title: Butyrate- but not TGFbeta1-induced apoptosis of colorectal adenoma cells is associated with increased expression of the differentiation markers E-cadherin and alkaline phosphatase.
abstract: Sodium butyrate and transforming growth factor beta (TGFbeta1) are growth inhibitory to colonic adenoma cell lines. Butyrate induces apoptosis, whereas in some adenoma cell lines, TGFbeta1 can be growth inhibitory without apoptosis. In this report, we show that the adenoma cell line PC/BH/C1 undergoes apoptosis in response to TGFbeta1. Butyrate induced cell death is preceded by the induction of two markers of colonic differentiation--alkaline phosphatase (ALP) activity and E-cadherin protein expression. However, TGFbeta1-induced apoptosis was not accompanied by induction of these differentiation markers. It is possible that the apoptosis induced by TGFbeta1 in the adenoma cell line PC/BH/C1 is due to conflicting signals, as downregulation of c-myc protein in response to TGFbeta1 occurs only slowly in this cell line. Development of resistance to TGFbeta1 in colonic tumours may involve two separate stages--resistance to growth inhibition and resistance to TGFbeta1-induced apoptosis. Our results indicate that sodium butyrate induces apoptosis via differentiation, but TGFbeta1 induces apoptosis by a differentiation-independent mechanism. As for butyrate, the induction of E-cadherin expression is a potentially important chemopreventative action, since increased E-cadherin expression has been correlated with decreased metastatic potential. This is the first report of induction of E-cadherin by a naturally occurring factor in the diet. Butyrate may reduce tumour growth and invasion, not only as a result of the induction of apoptosis, but also through increased expression of E-cadherin.
authors.affiliation: CRC Colorectal Tumour Biology Research Group, Department of Pathology and Microbiology, University of Bristol, School of Medical Sciences, University Walk, Bristol BS8 1TD, UK.
authors.forename: A J
authors.initials: AJ
authors.lastname: Butt
authors.forename: A
authors.initials: A
authors.lastname: Hague
authors.forename: C
authors.initials: C
authors.lastname: Paraskeva