Apoptotic human neutrophil peptide-1 anti-tumor activity revealed by cellular biomechanics
Apoptotic human neutrophil peptide-1 anti-tumor activity revealed by cellular biomechanics
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DOI：
10.1016/j.bbamcr.2014.11.006
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发表时间：
2015-02-01
影响因子：
5.1
通讯作者：
Castanho, Miguel A. R. B.
中科院分区：
文献类型：
--
作者：
Gaspar, Diana;Freire, Joao M.;Castanho, Miguel A. R. B.
癌症仍然是全世界发病率和死亡率的主要原因。尽管在化疗药物方面取得了进展，但仍然需要将更高的选择性和有效性与低耐药性结合起来的新疗法。在寻找新的抗癌药物的过程中，基于生物活性肽，特别是抗菌肽（AMPs）的治疗方法因其降低耐药性和低细胞毒性而受到关注。许多amp已被证明是针对人类癌细胞的杀瘤剂，但其作用方式仍存在争议。细菌和肿瘤细胞膜共有的共同特性指出，在这两种情况下，类似的脂质靶向机制。另一方面，抗肿瘤肽（ACPs）还能诱导细胞凋亡和抑制血管生成。人中性粒细胞肽-1 （HNP-1）是一种内源性AMP，与肿瘤增殖等不同的细胞现象有关。肿瘤患者血清/血浆中HNP-1的存在使这种肽成为一种潜在的肿瘤生物标志物。本研究揭示了HNP-1对实体和血液学肿瘤细胞的生物物理和纳米力学特性的不同影响。利用原子力显微镜（AFM）和zeta电位测量对细胞形态学、细胞刚度、膜超微结构和电荷的研究表明，与人白血病细胞相比，HNP-1与人前列腺腺癌实体瘤细胞的结合更优先。AFM还显示，在非常低的肽浓度下，细胞膜缺陷诱导凋亡。了解ACPs的作用模式必将为癌症治疗药物开发开辟创新途径。(C) 2014 Elsevier B.V.版权所有
Cancer remains a major cause of morbidity and mortality worldwide. Although progress has been made regarding chemotherapeutic agents, new therapies that combine increased selectivity and efficacy with low resistance are still needed. In the search for new anticancer agents, therapies based on biologically active peptides, in particular, antimicrobial peptides (AMPs), have attracted attention for their decreased resistance development and low cytotoxicity. Many AMPs have proved to be tumoricidal agents against human cancer cells, but their mode of action is still controversial. The existence of common properties shared by the membranes of bacteria and tumor cells points to similar lipid-targeting mechanisms in both cases. On the other hand, anticancer peptides (ACPs) also induce apoptosis and inhibit angiogenesis. Human neutrophil peptide-1 (HNP-1) is an endogenous AMP that has been implicated in different cellular phenomena such as tumor proliferation. The presence of HNP-1 in the serum/plasma of oncologic patients turns this peptide into a potential tumor biomarker. The present work reveals the different effects of HNP-1 on the biophysical and nanomechanical properties of solid and hematological tumor cells. Studies on cellular morphology, cellular stiffness, and membrane ultrastructure and charge using atomic force microscopy (AFM) and zeta potential measurements show a preferential binding of HNP-1 to solid tumor cells from human prostate adenocarcinoma when compared to human leukemia cells. AFM also reveals induction of apoptosis with cellular membrane defects at very low peptide concentrations. Understanding ACPs mode(s) of action will certainly open innovative pathways for drug development in cancer treatment. (C) 2014 Elsevier B.V. All rights reserved.