Milena Mechkarska , Samir Attoub , Shahrazad Sulaiman , Jelena Pantic , Miodrag L. Lukic , J. Michael Conlon
{"title":"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","authors":"Milena Mechkarska , Samir Attoub , Shahrazad Sulaiman , Jelena Pantic , Miodrag L. Lukic , J. Michael Conlon","doi":"10.1016/j.regpep.2014.11.001","DOIUrl":null,"url":null,"abstract":"<div><p><span>Pseudhymenochirin-1Pb (Ps-1Pb) and pseudhymenochirin-2Pa (Ps-2Pa) are host-defense peptides, first isolated from skin secretions of the frog </span><em>Pseudhymenochirus merlini</em> (Pipidae). Ps-1Pb and Ps-2Pa are highly cytotoxic (LC<sub>50</sub> <!--><<!--> <!-->12<!--> <span>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 (LC</span><sub>50</sub> <!-->=<!--> <!-->28<!--> <!-->±<!--> <!-->2<!--> <!-->μM for Ps-1Pb and LC<sub>50</sub> <!-->=<!--> <!-->6<!--> <!-->±<!--> <!-->1<!--> <!-->μM for Ps-2Pa). Ps-2Pa shows selective cytotoxicity for tumor cells (LC<sub>50</sub><span> against non-neoplastic human umbilical vein (HUVEC) cells</span> <!-->=<!--> <!-->68<!--> <!-->±<!--> <!-->2<!--> <!-->μM). Ps-1Pb and Ps-2Pa (5<!--> <span>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</span> <!-->≤<!--> <!-->10<!--> <!-->μM) inhibits growth of multidrug-resistant clinical isolates of the Gram-positive bacteria methicillin-resistant <em>Staphylococcus aureus</em> and <span><em>Staphylococcus epidermidis</em></span>, and the Gram-negative bacteria <span><em>Acinetobacter</em><em> baumannii</em></span> and <span><em>Stenotrophomonas maltophilia</em></span>.</p><p>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 <em>Escherichia coli</em> within 30<!--> <!-->min and 99.9% of <em>S. aureus</em> within 180<!--> <span>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.</span></p></div>","PeriodicalId":20853,"journal":{"name":"Regulatory Peptides","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2014-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.regpep.2014.11.001","citationCount":"33","resultStr":"{\"title\":\"Anti-cancer, immunoregulatory, and antimicrobial activities of the frog skin host-defense peptides pseudhymenochirin-1Pb and pseudhymenochirin-2Pa\",\"authors\":\"Milena Mechkarska , Samir Attoub , Shahrazad Sulaiman , Jelena Pantic , Miodrag L. Lukic , J. Michael Conlon\",\"doi\":\"10.1016/j.regpep.2014.11.001\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p><span>Pseudhymenochirin-1Pb (Ps-1Pb) and pseudhymenochirin-2Pa (Ps-2Pa) are host-defense peptides, first isolated from skin secretions of the frog </span><em>Pseudhymenochirus merlini</em> (Pipidae). Ps-1Pb and Ps-2Pa are highly cytotoxic (LC<sub>50</sub> <!--><<!--> <!-->12<!--> <span>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 (LC</span><sub>50</sub> <!-->=<!--> <!-->28<!--> <!-->±<!--> <!-->2<!--> <!-->μM for Ps-1Pb and LC<sub>50</sub> <!-->=<!--> <!-->6<!--> <!-->±<!--> <!-->1<!--> <!-->μM for Ps-2Pa). Ps-2Pa shows selective cytotoxicity for tumor cells (LC<sub>50</sub><span> against non-neoplastic human umbilical vein (HUVEC) cells</span> <!-->=<!--> <!-->68<!--> <!-->±<!--> <!-->2<!--> <!-->μM). Ps-1Pb and Ps-2Pa (5<!--> <span>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</span> <!-->≤<!--> <!-->10<!--> <!-->μM) inhibits growth of multidrug-resistant clinical isolates of the Gram-positive bacteria methicillin-resistant <em>Staphylococcus aureus</em> and <span><em>Staphylococcus epidermidis</em></span>, and the Gram-negative bacteria <span><em>Acinetobacter</em><em> baumannii</em></span> and <span><em>Stenotrophomonas maltophilia</em></span>.</p><p>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 <em>Escherichia coli</em> within 30<!--> <!-->min and 99.9% of <em>S. aureus</em> within 180<!--> <span>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.</span></p></div>\",\"PeriodicalId\":20853,\"journal\":{\"name\":\"Regulatory Peptides\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2014-11-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://sci-hub-pdf.com/10.1016/j.regpep.2014.11.001\",\"citationCount\":\"33\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Regulatory Peptides\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0167011514000846\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Regulatory Peptides","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0167011514000846","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
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.
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.