美國伊利諾伊州立大學(xué)的科學(xué)家成功合成出一種可以讓腫瘤細(xì)胞自行凋亡的分子?！ ?nbsp;
在罹患腫瘤疾病期間,，有缺陷細(xì)胞按程序凋亡的過程被破壞，癌變細(xì)胞能夠?qū)箼C(jī)體發(fā)出的凋亡信號，這樣癌變細(xì)胞就可以毫無監(jiān)控地分裂,，并形成腫瘤,。
根據(jù)科學(xué)家們掌握的證據(jù)，癌變細(xì)胞的這種能力與半胱天冬酶-3（caspase-3）的缺失有關(guān),，這種蛋白酶參與到細(xì)胞凋亡過程中,。由于癌變細(xì)胞中半胱天冬酶-3酶原蛋白(procaspase-3)形成caspase-3的過程被破壞，所以這種蛋白酶的數(shù)量不足,。
保羅·赫根羅德(Paul Hergenrother)領(lǐng)導(dǎo)的科學(xué)家團(tuán)隊(duì)研究了超過兩萬種化合物以尋找到能夠促進(jìn)半胱天冬酶-3酶原蛋白合成半胱天冬酶-3的物質(zhì),。終于科學(xué)家們找到了這種化合物。合成分子PAC-1能夠促進(jìn)半胱天冬酶-3的形成,。同時(shí),，它還激活了從小鼠和人類腫瘤中分離出來的癌變細(xì)胞的自然死亡的過程。
PAC-1主要是針對那些procaspase-3含量較高的細(xì)胞發(fā)揮作用,。在腸,、皮膚、肝臟等部位的腫瘤細(xì)胞及白血病細(xì)胞中這種蛋白的含量較高,。同時(shí),，健康細(xì)胞對于PAC-1的作用并不敏感，因?yàn)榻】导?xì)胞中procaspase-3的含量并不高,。研究人員指出,，通過對同一個(gè)腫瘤患者的正常細(xì)胞與腫瘤細(xì)胞進(jìn)行化驗(yàn)表明，癌變細(xì)胞對PAC-1的敏感程度要高２０００倍,。
保羅·赫根羅德指出,，“我們可以預(yù)測出像PAC-1這樣的化合物的潛在能力。”他還補(bǔ)充說,，他們將選擇一些腫瘤細(xì)胞中procaspase-3的含量水平較高的患者進(jìn)行治療,。
科學(xué)家計(jì)劃在以后將要進(jìn)行臨床研究以評估PAC-1的安全性?？茖W(xué)家指出,，在沒有發(fā)現(xiàn)嚴(yán)重的副作用的情況下，原則上醫(yī)生們將獲得一種治療腫瘤的新方法,。
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.
