美国伊利诺伊州立大学的科学家成功合成出一种可以让肿瘤细胞自行凋亡的分子。
在罹患肿瘤疾病期间，有缺陷细胞按程序凋亡的过程被破坏，癌变细胞能够对抗机体发出的凋亡信号，这样癌变细胞就可以毫无监控地分裂，并形成肿瘤。
根据科学家们掌握的证据，癌变细胞的这种能力与半胱天冬酶-3（caspase-3）的缺失有关，这种蛋白酶参与到细胞凋亡过程中。由于癌变细胞中半胱天冬酶-3酶原蛋白(procaspase-3)形成caspase-3的过程被破坏，所以这种蛋白酶的数量不足。
保罗·赫根罗德(Paul Hergenrother)领导的科学家团队研究了超过两万种化合物以寻找到能够促进半胱天冬酶-3酶原蛋白合成半胱天冬酶-3的物质。终于科学家们找到了这种化合物。合成分子PAC-1能够促进半胱天冬酶-3的形成。同时，它还激活了从小鼠和人类肿瘤中分离出来的癌变细胞的自然死亡的过程。
PAC-1主要是针对那些procaspase-3含量较高的细胞发挥作用。在肠、皮肤、肝脏等部位的肿瘤细胞及白血病细胞中这种蛋白的含量较高。同时，健康细胞对于PAC-1的作用并不敏感，因为健康细胞中procaspase-3的含量并不高。研究人员指出，通过对同一个肿瘤患者的正常细胞与肿瘤细胞进行化验表明，癌变细胞对PAC-1的敏感程度要高２０００倍。
保罗·赫根罗德指出，“我们可以预测出像PAC-1这样的化合物的潜在能力。”他还补充说，他们将选择一些肿瘤细胞中procaspase-3的含量水平较高的患者进行治疗。
科学家计划在以后将要进行临床研究以评估PAC-1的安全性。科学家指出，在没有发现严重的副作用的情况下，原则上医生们将获得一种治疗肿瘤的新方法。
英文原文：
Synthetic molecule causes cancer cells to self-destruct
CHAMPAIGN, Ill. -- Scientists have found a way to trick cancer cells into committing suicide. The novel technique potentially offers an effective method of providing personalized anti-cancer therapy. Most living cells contain a protein called procaspase-3, which, when activated, changes into the executioner enzyme caspase-3 and initiates programmed cell death, called apoptosis. In cancer cells, however, the signaling pathway to procaspase-3 is broken. As a result, cancer cells escape destruction and grow into tumors.
"We have identified a small, synthetic compound that directly activates procaspase-3 and induces apoptosis," said Paul J. Hergenrother, a professor of chemistry at the University of Illinois at Urbana-Champaign and corresponding author of a paper to be posted online this week ahead of regular publication by the journal Nature Chemical Biology. "By bypassing the broken pathway, we can use the cells' own machinery to destroy themselves."
To find the compound, called procaspase activating compound one (PAC-1), Hergenrother, with colleagues at the U. of I., Seoul National University, and the National Center for Toxicological Research, screened more than 20,000 structurally diverse compounds for the ability to change procaspase-3 into caspase-3.
The researchers tested the compound's efficacy in cell cultures and in three mouse models of cancer. The testing was performed in collaboration with William Helferich, a professor of food science and human nutrition at the U. of I., and Myung-Haing Cho at Seoul National University. The researchers also showed that PAC-1 killed cancer cells in 23 tumors obtained from a local hospital.
Cell death was correlated with the level of procaspase-3 present in the cells, with more procaspase-3 resulting in cell death at lower concentrations of PAC-1.
"This is the first in what could be a host of organic compounds with the ability to directly activate executioner enzymes," said Hergenrother, who is also an affiliate of the Institute for Genomic Biology at the U. of I. "The potential effectiveness of compounds such as PAC-1 could be predicted in advance, and patients could be selected for treatment based on the amount of procaspase-3 found in their tumor cells."
Such personalized medicine strategies are preferential to therapies that rely on general cytotoxins, the researchers say, and could be the future of anti-cancer therapy.
