Darkin S, McQuillan J, Ralph R K
Biochem Biophys Res Commun. 1984 Nov 30;125(1):184-91. doi: 10.1016/s0006-291x(84)80352-6.
The antipsychotic drug chlorpromazine causes scission of the DNA in PY815 mouse mastocytoma cells or isolated PY815 cell nuclei and the broken DNA reseals when chlorpromazine is removed from nuclei. These properties suggest that chlorpromazine interferes with topoisomerase action as do several other DNA-intercalating anti-cancer drugs. However, protein is not associated with the broken DNA after chlorpromazine treatment suggesting a different mode of action on the topoisomerase. Reasons why chlorpromazine may have potential as anti-cancer agent are considered.
抗精神病药物氯丙嗪可导致PY815小鼠肥大细胞瘤细胞或分离出的PY815细胞核中的DNA断裂,当从细胞核中去除氯丙嗪时,断裂的DNA会重新封闭。这些特性表明,氯丙嗪与其他几种DNA嵌入型抗癌药物一样,会干扰拓扑异构酶的作用。然而,氯丙嗪处理后,断裂的DNA上并未发现蛋白质,这表明其对拓扑异构酶的作用方式有所不同。文中还探讨了氯丙嗪可能具有抗癌潜力的原因。