Carlson C C, Burnham L L, Shanks R A, Dransfield D T
Department of General Surgery, Medical College of Georgia, Atlanta 30912, USA [corrected].
Dig Dis Sci. 2001 Apr;46(4):757-64. doi: 10.1023/a:1010740015072.
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.
8-氯腺苷是一种新型无毒化疗药物，已证明可抑制多种结肠癌细胞系的生长。我们利用分泌粘蛋白的结肠癌细胞系LS174T，来评估8-氯腺苷独立于其母体化合物8-氯环磷酸腺苷（8-Cl-cAMP）的生长抑制特性。在LS174T细胞中，8-氯环磷酸腺苷向8-氯腺苷的转化是生长抑制所必需的。8-氯腺苷通过诱导G1期细胞周期停滞来抑制生长，这与p21WAF1/Cip1和p53蛋白水平大幅（八倍）增加以及视网膜母细胞瘤蛋白磷酸化状态降低有关。LS174T细胞未发生凋亡。此外，8-氯腺苷还诱导了一定程度的肠细胞分化。用8-氯腺苷处理后，绒毛蛋白水平以及碱性磷酸酶活性均升高（分别为2倍和3.5倍）。我们的结果表明，在LS174T细胞中，8-氯腺苷不仅是一种生长抑制剂，也是一种肠细胞分化诱导剂。
