蛙皮肤宿主防御肽pseudhymenochirin-1Pb和pseudhymenochirin-2Pa的抗癌、免疫调节和抗菌活性

Milena Mechkarska , Samir Attoub , Shahrazad Sulaiman , Jelena Pantic , Miodrag L. Lukic , J. Michael Conlon
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引用次数: 33

摘要

Pseudhymenochirin-1Pb (Ps-1Pb)和pseudhymenochirin-2Pa (Ps-2Pa)是首次从蛙类merlini Pseudhymenochirus merlini (Pipidae)的皮肤分泌物中分离得到的宿主防御肽。Ps-1Pb和Ps-2Pa具有高细胞毒性(LC50 <12 μM)对非小细胞肺腺癌A549细胞、乳腺腺癌MDA-MB-231细胞、结直肠腺癌HT-29细胞也有溶血作用(Ps-1Pb LC50 = 28±2 μM, Ps-2Pa LC50 = 6±1 μM)。Ps-2Pa对肿瘤细胞具有选择性细胞毒性(对非肿瘤性人脐静脉(HUVEC)细胞的LC50 = 68±2 μM)。Ps-1Pb和Ps-2Pa (5 μg/mL)显著抑制脂多糖刺激的C57BL/6小鼠腹腔巨噬细胞产生抗炎细胞因子IL-10和多功能细胞因子IL-6,增强未刺激和LPS刺激的巨噬细胞产生促炎细胞因子IL-23。Ps-1Pb对革兰氏阳性菌耐甲氧西林金黄色葡萄球菌和表皮葡萄球菌,以及革兰氏阴性菌鲍曼不动杆菌和嗜麦芽寡养单胞菌的临床多药分离株的生长有较强的抑制作用(MIC≤10 μM),但对革兰氏阴性菌的抑制作用弱2-4倍。4倍MIC的Ps-1Pb在30分钟内杀死99.9%的大肠杆菌,在180分钟内杀死99.9%的金黄色葡萄球菌。总之,对肿瘤细胞的细胞毒性、细胞因子介导的免疫调节特性和广谱抗菌活性表明,Ps-1Pb和Ps-2Pa为设计用于肿瘤治疗的非溶血性类似物和治疗由多重耐药病原体产生的癌症患者感染提供了模板。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Anti-cancer, immunoregulatory, and antimicrobial activities of the frog skin host-defense peptides pseudhymenochirin-1Pb and pseudhymenochirin-2Pa

Pseudhymenochirin-1Pb (Ps-1Pb) and pseudhymenochirin-2Pa (Ps-2Pa) are host-defense peptides, first isolated from skin secretions of the frog Pseudhymenochirus merlini (Pipidae). Ps-1Pb and Ps-2Pa are highly cytotoxic (LC50 < 12 μM) against non-small cell lung adenocarcinoma A549 cells, breast adenocarcinoma MDA-MB-231 cells, and colorectal adenocarcinoma HT-29 cells but are also hemolytic against human erythrocytes (LC50 = 28 ± 2 μM for Ps-1Pb and LC50 = 6 ± 1 μM for Ps-2Pa). Ps-2Pa shows selective cytotoxicity for tumor cells (LC50 against non-neoplastic human umbilical vein (HUVEC) cells = 68 ± 2 μM). Ps-1Pb and Ps-2Pa (5 μg/mL) significantly inhibit production of the anti-inflammatory cytokine IL-10 and the multifunctional cytokine IL-6 from lipopolysaccharide (LPS)-stimulated peritoneal macrophages from C57BL/6 mice and enhance the production of the pro-inflammatory cytokine IL-23 from both unstimulated and LPS-stimulated macrophages. Ps-1Pb potently (MIC  10 μM) inhibits growth of multidrug-resistant clinical isolates of the Gram-positive bacteria methicillin-resistant Staphylococcus aureus and Staphylococcus epidermidis, and the Gram-negative bacteria Acinetobacter baumannii and Stenotrophomonas maltophilia.

Ps-2Pa shows the same high potency (MIC  10 μM) against the Gram-positive bacteria but is 2–4 fold less potent against the Gram-negative isolates. Ps-1Pb at 4 × MIC kills 99.9% of Escherichia coli within 30 min and 99.9% of S. aureus within 180 min. In conclusion, cytotoxicity against tumor cells, cytokine-mediated immunomodulatory properties, and broad-spectrum antimicrobial activity suggest that the Ps-1Pb and Ps-2Pa represent templates for design of non-hemolytic analogs for tumor therapy and for treatment of infections in cancer patients produced by multidrug-resistant pathogens.

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来源期刊
Regulatory Peptides
Regulatory Peptides 医学-内分泌学与代谢
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2 months
期刊介绍: Regulatory Peptides provides a medium for the rapid publication of interdisciplinary studies on the physiology and pathology of peptides of the gut, endocrine and nervous systems which regulate cell or tissue function. Articles emphasizing these objectives may be based on either fundamental or clinical observations obtained through the disciplines of morphology, cytochemistry, biochemistry, physiology, pathology, pharmacology or psychology.
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