期刊
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
卷 1860, 期 11, 页码 2155-2165出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.bbamem.2018.08.012
关键词
Helical antimicrobial peptides; Chemotherapy; Breast tumor-cells; Cytotoxic activity; Flow cytometry; Membranes; Biophysical studies; Leakage; LUV; DSC
资金
- Coordination for the Improvement of Higher Education Personnel (CAPES-PNPD) [23038.007147/2011-60]
- Sao Paulo Research Foundation (FAPESP) [2014/00206-0, 2014/18747-8]
- Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)
Antimicrobial peptides have been extensively described as bioactive agents, mainly considering their selective toxicity towards bacteria but not to healthy mammalian cells. In past years, this class of compounds has been classified as an attractive and novel family of anticancer agents. Pantinin peptides isolated from scorpion Pandinus imperator presented antimicrobial activity. In this study, we have explored the in vitro antitumor activity of antimicrobial pantinin peptides against the tumor cell lines MDA-MB-231 (breast adenocarcinoma) and DU - 145 (prostate adenocarcinoma) and healthy fibroblasts HGF - 1. To further improve our mechanistic understanding for this class of compounds, we have also performed a biophysical characterization of these peptides in lipid model membranes. Cell viability assays revealed that all peptides were more effective on tumor cells when compared to fibroblasts, indicating selectivity towards cancer cells. Furthermore, flow cytometry analysis revealed that all peptides induced apoptosis in cancer cells in a different way from fibroblasts. Circular dichroism spectroscopy showed that all peptides adopted an alpha-helical structure and an evaluation of the binding constant indicates a higher affinity of the peptides to negatively charged phospholipids. Additionally, permeabilization assays showed that POPG and POPS anionic vesicles were more susceptible to peptide-induced lysis than POPC:Chol and POPC:POPE vesicles. Moreover, we have observed that increasing concentrations of cholesterol inhibits peptide binding process. Therefore, our findings suggest that Pantinin peptides may have chemotherapeutic potential for cancer treatment.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据