Amphipathic tail-anchoring peptide is a promising therapeutic agent for prostate cancer treatment.
Amphipathic tail-anchoring peptide is a promising therapeutic agent for prostate cancer treatment.
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DOI：
10.18632/oncotarget.2301
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发表时间：
2014-09-15
期刊：
影响因子：
--
通讯作者：
Ma J
中科院分区：
文献类型：
--
作者：
De G;Ko JK;Tan T;Zhu H;Li H;Ma J
两亲性尾锚定多肽(ATAP)来源于人类抗凋亡蛋白BFL-1，通过靶向线粒体通透性转换而成为一种有效的细胞凋亡诱导剂。通过将ATAP与内化RGD肽(IRGD)连接，实现了ATAP对肿瘤细胞的选择性靶向。共聚焦荧光显微镜显示ATAP-IRGD可穿透癌细胞并沿线粒体网络分布。ATAP-IRGD通过释放细胞色素c导致线粒体依赖性细胞死亡。为了促进ATAP-IRGD的理化性质接近临床应用，对ATAP-IRGD进行了氨基酸取代和化学修饰，以提高其生物活性。其中一种经修饰的多肽ATAP-IRGD-M8具有更好的稳定性和在水中的溶解性，而不影响体外培养的癌细胞的细胞毒性。体内对多种前列腺癌细胞系的异种移植研究表明，静脉注射ATAP-IRGD-M8抑制了肿瘤的生长。毒理学研究表明，重复静脉注射ATAP-IRGD-M8对SV129小鼠没有明显毒性。我们的数据表明ATAP-IRGD-M8是一种选择性高、全身毒性有限的前列腺癌治疗药物。
Amphipathic tail-anchoring peptide (ATAP) derived from the human anti-apoptotic protein Bfl-1 is a potent inducer of apoptosis by targeting mitochondria permeability transition. By linking ATAP to an internalizing RGD peptide (iRGD), selective targeting for ATAP to tumor cell was achieved. Confocal fluorescence microscopy showed that ATAP-iRGD could penetrate into cancer cells and distribute along the mitochondria network. ATAP-iRGD triggered mitochondria-dependent cell death through release of cytochrome c. In an effort to promote ATAP-iRGD physiochemical properties to approach clinic application, amino acid substitution and chemical modification were made with ATAP-iRGD to improve its bioactivity. One of these modified peptides, ATAP-iRGD-M8, was with improved stability and aqueous solubility without compromising in vitro cytotoxicity in cultured cancer cells. In vivo xenograft studies with multiple prostate cancer cell lines showed that intravenous administration of ATAP-iRGD-M8 suppressed tumor growth. Toxicological studies revealed that repetitive intravenous administration of ATAP-iRGD-M8 did not produce significant toxicity in the SV129 mice. Our data suggest that ATAP-iRGD-M8 is a promising agent with high selectivity and limited systemic toxicity for prostate cancer treatment.
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影响因子：
64.8
作者：
Pasqualini, R;Ruoslahti, E
通讯作者：
Ruoslahti, E
DOI：
10.1073/pnas.250299897
发表时间：
2000-12-19
影响因子：
11.1
作者：
Guerrero, CA;Méndez, E;Arias, CF
通讯作者：
Arias, CF
影响因子：
64.5
作者：
PYTELA, R;PIERSCHBACHER, MD;RUOSLAHTI, E
通讯作者：
RUOSLAHTI, E
影响因子：
4.8
作者：
Ko, Jae-Kyun;Choi, Kyoung-Han;Ma, Jianjie
通讯作者：
Ma, Jianjie
影响因子：
1.7
作者：
Smolarczyk, Ryszard;Cichon, Tomasz;Szala, Stanislaw
通讯作者：
Szala, Stanislaw