8-Cl-adenosine induces differentiation in LS174T cells

8-Cl-adenosine represents a novel nontoxic chemotherapeutic agent shown to inhibit growth of a number of colorectal cancer cell lines. We have utilize d the mucin-secreting colorectal cancer cell line, LS174T, to assess the gr owth inhibitory properties of 8-Cl-adenosine independent of its parental co mpound, 8-Cl-cAMP. Conversion of 8-Cl-cAMP to 8-Cl-adenosine is required fo r growth inhibition in LS174T cells. 8-Cl-Adenosine inhibited growth by ind ucing a G, cell cycle arrest that was associated with large (eightfold) inc reases in p21(WAF1/Cipl) and p53 protein levels and a decrease in the phosp horylation status of the retinoblastoma protein. LS174T cells did not under go apoptosis. In addition, 8-Cl-adenosine also induced some degree of enter ocytic differentiation. Both villin protein levels as well as alkaline phos phatase activity rose (2- and 3.5-fold, respectively) in response to treatm ent with 8-Cl-adenosine, Our results suggest that in LS174T cells, 8-Cl-ade nosine not only serves as a growth inhibitory agent but also as an inducer of enterocytic differentiation.