Induction of tissue transglutaminase expression by propionate and n-butyrate in colon cancer cell lines.
Short-chain fatty acids (SCFAs) have been demonstrated to induce differentiation and/or apoptosis in colon cancer cells. A close correlation between tissue transglutaminase (tTG) expression and differentiation and/or apoptosis has been suggested in many cell lineages. However, the effects of SCFAs on tTG expression in colon cancer cells have not yet been reported. In this report, the relationship between cytosolic tTG levels and differentiation state was investigated in six human colon cancer cell lines. Effects of four kinds of SCFAs (acetate, propionate, n-butyrate, and isobutyrate) on the expression of tTG then were investigated in association with their effects on apoptosis induction. High expression of tTG protein and mRNA were found in SW480 and WiDr cell lines, which exhibited well differentiated phenotypes. tTG expression was hardly detectable in the less differentiated cell lines COLO201, COLO320DM, and CW-2. However, n-butyrate and propionate significantly increased cytosolic tTG levels at concentrations above 0.5 mM in these less differentiated colon cancer cells. n-Butyrate and propionate induced growth suppression and apoptosis in these cell lines at concentrations that can induce tTG expression. Acetate and isobutyrate did not induce tTG expression or growth suppression at concentrations up to 8 mM. In conclusion, tTG induction by propionate and n-butyrate was suggested to be closely linked to their differentiation- and apoptosis-inducing effects in colon cancer cells. These findings may explain the mechanisms by which dietary fiber show preventive effects against colon carcinogenesis.
Fukuda
K
K
Department of Oriental Medicine, Gifu University School of Medicine, Gifu, Japan.