用一種小分子“喚醒”能導致細胞死亡的關(guān)鍵酶caspase-3，科學家們發(fā)現(xiàn)了一種可讓某些癌細胞自我毀滅的方法,。他們在10月出版的《自然—化學生物學》期刊上報告了這種新方法,。
通常情況下,，caspase-3以原酶的形式存在，也就是說需要有進一步的程序才能使之成為活性酶,。這個過程一般是由其他蛋白酶caspase來執(zhí)行,，當細胞出現(xiàn)問題時，caspase以信號的形式提供服務,。這種信號的出現(xiàn)表明需要細胞死亡或凋亡?，F(xiàn)在，Paul Hergenrother和同事利用合成化合物PAC-1來誘導procaspase-3進入程序化過程,，產(chǎn)生caspase-3讓細胞死亡。他們的研究表明,，在多種類型的癌細胞中,，細胞的死亡與細胞中 procaspase-3的水平有關(guān)。低劑量PAC-1就會產(chǎn)生更多的導致細胞死亡的procaspase-3,，同時卻不損害健康細胞,。
實驗表明，procaspase-3在不同個體細胞中的含量是不一樣的,，這也許會解釋為什么部分患者比其他患者對這種治療反應更強烈,。為癌癥患者提供因人而異的治療方法是一種夢想，新研究為之展示了一種新的可能性,。
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.
