Dosik G M, Barlogie B, Johnston D A, Murphy W K, Drewinko B
Cancer Res. 1978 Oct;38(10):3304-9.
Anguidine is a fungal metabolite with antitumor activity in a murine colon cancer model. Because of disappointing results in clinical trials, we analyzed the lethal and cytokinetic effects of anguidine on cultured human colon cancer cells. The studies revealed a moderate reduction in survival only after prolonged drug exposure. Continuous incubation with anguidine for longer than 48 hr produced a moderate increase in the percentage of S-phase cells and a slight decrease in the proportion of cells in G1/0, by pulse cytophotometry. An immediate reduction in the cumulative labeling index for cells continuously exposed to tritiated thymidine and anguidine and a rapid decrease in the cumulative mitotic index for cells continuously exposed to Colcemid and anguidine indicated a block at the G1 into S and G2 into mitosis transitions. Tumoricidal activity of anguidine in a cultured human colon cancer line is poor and requires prolonged exposure. The kinetic data reflect an almost frozen state of the cell cycle.
安圭定是一种在小鼠结肠癌模型中具有抗肿瘤活性的真菌代谢产物。由于临床试验结果令人失望，我们分析了安圭定对培养的人结肠癌细胞的致死和细胞动力学效应。研究表明，仅在长时间药物暴露后，细胞存活率才出现适度降低。通过脉冲细胞光度法，用安圭定连续孵育超过48小时后，S期细胞百分比适度增加，G1/0期细胞比例略有下降。连续暴露于氚标记胸腺嘧啶核苷和安圭定的细胞的累积标记指数立即降低，以及连续暴露于秋水仙酰胺和安圭定的细胞的累积有丝分裂指数迅速下降，表明在G1期向S期以及G2期向有丝分裂期的转变过程中出现了阻滞。安圭定在培养的人结肠癌细胞系中的杀瘤活性较差，需要长时间暴露。动力学数据反映了细胞周期几乎处于停滞状态。
