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 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.
Carlson
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CC
Department of General Surgery, Medical College of Georgia, Atlanta 30912, USA [corrected].
Burnham
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LL
Shanks
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Dransfield
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D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000031:analogs & derivatives* / Q000378:metabolism; D000241:Adenosine / Q000378:metabolism / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000473:pathology*; D006801:Humans; D015689:Oncogene Protein p21(ras) / Q000096:biosynthesis; D013997:Time Factors; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis
D016159:Tumor Suppressor Protein p53; D015124:8-Bromo Cyclic Adenosine Monophosphate; C044258:8-chloro-cyclic adenosine monophosphate; D015689:Oncogene Protein p21(ras); D000241:Adenosine