Mizushima T, Natori S, Sekimizu K
Faculty of Pharmaceutical Sciences, University of Tokyo, Japan.
Biol Pharm Bull. 1993 Oct;16(10):953-5. doi: 10.1248/bpb.16.953.
We examined the influence of chlorpromazine, a phenothiazine derivative, on DNA synthesis in Meth A cells. Pulse-labelling experiments with [3H]thymidine showed that chlorpromazine inhibited DNA synthesis in cells cultured in vitro. The drug also inhibited DNA synthesis in isolated nuclei. Observation by fluorescence microscopy of fibroblastic cells stained with chlorpromazine indicated that the drug was localized in the cytoplasm and nuclear membranes, suggesting that it inhibited DNA synthesis in a manner dependent on the interaction of replication proteins with nuclear membranes. Meth A sarcomas growing in the endoderm of BALB/c mice regressed on intra-tumor injection of chlorpromazine, indicating that the drug has an anticancer action.
我们研究了吩噻嗪衍生物氯丙嗪对Meth A细胞DNA合成的影响。用[3H]胸腺嘧啶进行的脉冲标记实验表明，氯丙嗪在体外培养的细胞中抑制DNA合成。该药物也抑制分离细胞核中的DNA合成。用氯丙嗪染色的成纤维细胞的荧光显微镜观察表明，该药物定位于细胞质和核膜，这表明它以依赖于复制蛋白与核膜相互作用的方式抑制DNA合成。在BALB/c小鼠内胚层中生长的Meth A肉瘤在瘤内注射氯丙嗪后消退，表明该药物具有抗癌作用。
