Antitumor effects, cell selectivity and structure-activity relationship of a novel antimicrobial peptide polybia-MPI
Antitumor effects, cell selectivity and structure-activity relationship of a novel antimicrobial peptide polybia-MPI
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DOI：
10.1016/j.peptides.2008.01.015
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发表时间：
2008-06-01
期刊：
影响因子：
3
通讯作者：
Wang, Rui
中科院分区：
文献类型：
--
作者：
Wang, Kai-rong;Zhang, Bang-zhi;Wang, Rui
从群蜂Polybia Paulista的毒液中分离纯化出一种新的抗菌肽Polybia-MPI。它对革兰氏阳性菌和革兰氏阴性菌都有很强的抗菌活性，但对大鼠红细胞没有溶血作用。到目前为止，还没有关于其对任何肿瘤细胞株的抗肿瘤作用的报道。在本研究中，我们合成了Polybia-MPI，并研究了其抗肿瘤效果和细胞选择性。我们的结果表明，虎杖-MPI通过形成孔道发挥了细胞毒性和抗增殖作用。它能选择性地抑制前列腺癌细胞和膀胱癌细胞的增殖，但对正常小鼠成纤维细胞的细胞毒性较低。此外，为了研究白藜芦醇的构效关系，设计并合成了三个L-Pro取代亮氨酸(7)、丙氨酸(8)和天冬氨酸(9)的类似物。Leu(7)或Asp(9)的L-Pro替代显著降低了α-螺旋构象的含量，而AlAs的L-Pro替代可彻底破坏α-螺旋构象。经L-Pro取代后，其抗肿瘤活性显著降低，表明多糖的α-螺旋构象对其抗肿瘤活性具有重要作用。综上所述，Polybia-MPI可能为前列腺癌和膀胱癌的治疗提供一种新的治疗策略，因为它对正常细胞的细胞毒性相对较低。(C)2008 Elsevier Inc.保留所有权利。
A novel antimicrobial peptide, polybia-MPI, was purified from the venom of the social wasp Polybia paulista. It has potent antimicrobial activity against both Gram-positive and Gram-negative bacteria, but causing no hemolysis to rat erythrocytes. To date, there is no report about its antitumor effects on any tumor cell lines. In this study we synthesized polybia-MPI and studied its antitumor efficacy and cell selectivity. Our results revealed that polybia-MPI exerts cytotoxic and antiproliferative efficacy by pore formation. It can selectively inhibit the proliferation of prostate and bladder cancer cells, but has lower cytotoxicity to normal murine fibroblasts. In addition, to investigate the structure-activity relationship of polybia-MPI, three analogs in which Leu(7), Ala(8) or Asp(9) replaced by L-Pro were designed and synthesized. L-Pro substitution of Leu(7) or Asp(9) significantly reduces the content of a-helix conformation, and L-Pro substitution of Alas can disrupt the a-helix conformation thoroughly. The L-Pro substitution induces a significant reduction of antitumor activity, indicating that the a-helix conformation of polybia-MPI is important for its antitumor activity. In summary, polybia-MPI may offer a novel therapeutic strategy in the treatment of prostate cancer and bladder cancer, considering its relatively lower cytoxicity to normal cells. (C) 2008 Elsevier Inc. All rights reserved.