Induction of alkaline phosphatase activity has provided a convenient marker for differentiation of colon cancer cells. The degree to which different histone deacetylase inhibitors induce alkaline phosphatase and dipeptidyl peptidase activities was compared in bladder and colon cancer cell lines. The objective was to determine whether bladder cancer cell lines that retain activities of the cell surface hydrolases exhibit regulatory effects similar to those previously observed in colon cancer cells. Effects of histone deacetylase inhibitors on growth and alkaline phosphatase and dipeptidyl peptidase activities were studied in three human colon cancer cells and three bladder cancer cell lines. Growth inhibition was observed with all the histone deacetylase inhibitors that were examined. There was variability in the induction of enzyme activity with different histone deacetylase inhibitors but when induction was observed it was greater for alkaline phosphatase than for dipeptidyl peptidase. The data suggested that regulation of alkaline phosphatase and dipeptidyl peptidase activities by histone deacetylase inhibitors can be similar in bladder and colon cancer cells. However, the functional role of the enzyme activities in bladderderived cells remains to be established.
The addiction of most cancer cells to the metabolism of glucose is well established. The metabolism by cancer cells of other saccharides is less well characterized. We have studied the impact of mono-and disaccharides on growth of human bladder and colon cancer cells. Substitution for glucose by other monosaccharides (fructose, galactose and mannose) resulted in similar growth in some cell lines, but growth was greatly diminished in others. HT29 colon cancer cells were the only cell line to have a substantial increased growth with trehalose. In those cell lines in which alkaline phosphatase activity could be induced after incubation with butyrate, induction was observed with any of the saccharides that were examined. For the Caco-2 and HT29 colon cancer cells, co-incubation with 2-deoxyglucose was more inhibitory for growth with fructose than with glucose as substrate. There was a similar situation with some bladder cancer cell lines (5637, HT1197 and RT4) whereas with other bladder cancer cells (HT1376, T24 and UM-UC-3) 2-deoxyglucose caused greater inhibition with glucose. It was apparent that maltose could enhance growth to an extent that was similar to that seen with glucose and was not seen with other disaccharides. The enhanced growth with maltose required maltase activity in serum added to growth medium. In conclusion, the stimulation of growth by saccharides exhibits considerable variability with different molecules.
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