用一种小分子“唤醒”能导致细胞死亡的关键酶caspase-3，科学家们发现了一种可让某些癌细胞自我毁灭的方法。他们在10月出版的《自然—化学生物学》期刊上报告了这种新方法。
通常情况下，caspase-3以原酶的形式存在，也就是说需要有进一步的程序才能使之成为活性酶。这个过程一般是由其他蛋白酶caspase来执行，当细胞出现问题时，caspase以信号的形式提供服务。这种信号的出现表明需要细胞死亡或凋亡。现在，Paul Hergenrother和同事利用合成化合物PAC-1来诱导procaspase-3进入程序化过程，产生caspase-3让细胞死亡。他们的研究表明，在多种类型的癌细胞中，细胞的死亡与细胞中 procaspase-3的水平有关。低剂量PAC-1就会产生更多的导致细胞死亡的procaspase-3，同时却不损害健康细胞。
实验表明，procaspase-3在不同个体细胞中的含量是不一样的，这也许会解释为什么部分患者比其他患者对这种治疗反应更强烈。为癌症患者提供因人而异的治疗方法是一种梦想，新研究为之展示了一种新的可能性。
英文原文：
Small-molecule activation of procaspase-3 to caspase-3 as a personalized anticancer strategy
Mutation and aberrant expression of apoptotic proteins are hallmarks of cancer. These changes prevent proapoptotic signals from being transmitted to executioner caspases, thereby averting apoptotic death and allowing cellular proliferation. Caspase-3 is the key executioner caspase, and it exists as an inactive zymogen that is activated by upstream signals. Notably, concentrations of procaspase-3 in certain cancerous cells are significantly higher than those in noncancerous controls. Here we report the identification of a small molecule (PAC-1) that directly activates procaspase-3 to caspase-3 in vitro and induces apoptosis in cancerous cells isolated from primary colon tumors in a manner directly proportional to the concentration of procaspase-3 inside these cells. We found that PAC-1 retarded the growth of tumors in three different mouse models of cancer, including two models in which PAC-1 was administered orally. PAC-1 is the first small molecule known to directly activate procaspase-3 to caspase-3, a transformation that allows induction of apoptosis even in cells that have defective apoptotic machinery. The direct activation of executioner caspases is an anticancer strategy that may prove beneficial in treating the many cancers in which procaspase-3 concentrations are elevated.
