8-Cl-adenosine induces differentiation in LS174T cells

Digestive Diseases and Sciences
C C CarlsonD T Dransfield

Abstract

8-Cl-adenosine represents a novel nontoxic chemotherapeutic agent shown to inhibit growth of a number of colorectal cancer cell lines. We have utilized the mucin-secreting colorectal cancer cell line, LS174T, to assess the growth inhibitory properties of 8-Cl-adenosine independent of its parental compound, 8-Cl-cAMP. Conversion of 8-Cl-cAMP to 8-Cl-adenosine is required for growth inhibition in LS174T cells. 8-Cl-Adenosine inhibited growth by inducing a G1 cell cycle arrest that was associated with large (eightfold) increases in p21WAF1/Cip1 and p53 protein levels and a decrease in the phosphorylation status of the retinoblastoma protein. LS174T cells did not undergo apoptosis. In addition, 8-Cl-adenosine also induced some degree of enterocytic differentiation. Both villin protein levels as well as alkaline phosphatase activity rose (2- and 3.5-fold, respectively) in response to treatment with 8-Cl-adenosine. Our results suggest that in LS174T cells, 8-Cl-adenosine not only serves as a growth inhibitory agent but also as an inducer of enterocytic differentiation.

Citations

Jun 29, 2006·Molecular Reproduction and Development·Stephen M Downs, Jing Chen
Jul 31, 2009·Breast Cancer Research and Treatment·Christine M StellrechtVarsha Gandhi
Jan 21, 2006·World Journal of Gastroenterology : WJG·Hong-Mei WangYi-Ling Wang

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