Usnic acid causes apoptotic-like death in Leishmania major, L. infantum and L. tropica

Leishmaniasis, a deadly parasitic infection, threatens many people worldwide. Since the high cost, toxicity, and resistance are drawbacks of current treatment options, it is necessary to find safer and more effective new antileishmanial drugs. The aim of this study was to determine the antileishmani...

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Veröffentlicht in:	3 Biotech 2018-09, Vol.8 (9), p.384-7, Article 384
Hauptverfasser:	Derici, Mehmet Kürşat, Cansaran-Duman, Demet, Taylan-Özkan, Ayşegül
Format:	Artikel
Sprache:	eng
Schlagworte:	Acids Agriculture Animal models antileishmanial properties antileishmanials Apoptosis Bcl-2 protein Bioinformatics Biomaterials Biotechnology Cancer Research Chemical compounds Chemistry Chemistry and Materials Science death Gene expression gene expression regulation genes inhibitory concentration 50 Leishmania Leishmania major Leishmaniasis Original Original Article p53 Protein Parasitic diseases Pharmacology Promastigotes quantitative polymerase chain reaction reverse transcriptase polymerase chain reaction Stem Cells therapeutics Toxicity Usnic acid
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description	Leishmaniasis, a deadly parasitic infection, threatens many people worldwide. Since the high cost, toxicity, and resistance are drawbacks of current treatment options, it is necessary to find safer and more effective new antileishmanial drugs. The aim of this study was to determine the antileishmanial activity of usnic acid and its apoptotic mechanism on Leishmania spp. promastigotes. The antileishmanial activity was evaluated by MTT assay and apoptosis-related gene expression was investigated by qRT-PCR. Usnic acid was to be effective against Leishmania major, L. infantum , and L. tropica promastigotes at IC 50 = 10.76 µg/ml, 13.34 µg/ml, and 21.06 µg/ml, respectively. We also demonstrated a novel mechanism by which usnic acid inhibited proliferation and caused apoptosis; usnic acid upregulated p53, Bax, Casp-3 , and Casp-9 gene expression and downregulated the level of Bcl-2 gene expression. Accordingly, the expression level of the P53 gene increased in L. major, L. infantum and L. tropica by 14.4-, 11.8-, and 9.5-fold, respectively, and in contrast, the Bcl-2 gene expression decreased in all three leishmaniasis by 0.8-, 0.8-, and 0.7-fold, respectively. The present study, therefore, revealed that usnic acid played a critical role in the usnic acid-induced apoptotic process in Leishmania species. Usnic acid is easily accessible and an inexpensive agent, and can be considered as an alternative therapeutic agent for Leishmania infections subject to further tests in animal models.
doi_str_mv	10.1007/s13205-018-1409-6
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Since the high cost, toxicity, and resistance are drawbacks of current treatment options, it is necessary to find safer and more effective new antileishmanial drugs. The aim of this study was to determine the antileishmanial activity of usnic acid and its apoptotic mechanism on Leishmania spp. promastigotes. The antileishmanial activity was evaluated by MTT assay and apoptosis-related gene expression was investigated by qRT-PCR. Usnic acid was to be effective against Leishmania major, L. infantum , and L. tropica promastigotes at IC 50 = 10.76 µg/ml, 13.34 µg/ml, and 21.06 µg/ml, respectively. We also demonstrated a novel mechanism by which usnic acid inhibited proliferation and caused apoptosis; usnic acid upregulated p53, Bax, Casp-3 , and Casp-9 gene expression and downregulated the level of Bcl-2 gene expression. Accordingly, the expression level of the P53 gene increased in L. major, L. infantum and L. tropica by 14.4-, 11.8-, and 9.5-fold, respectively, and in contrast, the Bcl-2 gene expression decreased in all three leishmaniasis by 0.8-, 0.8-, and 0.7-fold, respectively. The present study, therefore, revealed that usnic acid played a critical role in the usnic acid-induced apoptotic process in Leishmania species. Usnic acid is easily accessible and an inexpensive agent, and can be considered as an alternative therapeutic agent for Leishmania infections subject to further tests in animal models.</description><identifier>ISSN: 2190-572X</identifier><identifier>EISSN: 2190-5738</identifier><identifier>DOI: 10.1007/s13205-018-1409-6</identifier><identifier>PMID: 30148034</identifier><language>eng</language><publisher>Cham: Springer International Publishing</publisher><subject>Acids ; Agriculture ; Animal models ; antileishmanial properties ; antileishmanials ; Apoptosis ; Bcl-2 protein ; Bioinformatics ; Biomaterials ; Biotechnology ; Cancer Research ; Chemical compounds ; Chemistry ; Chemistry and Materials Science ; death ; Gene expression ; gene expression regulation ; genes ; inhibitory concentration 50 ; Leishmania ; Leishmania major ; Leishmaniasis ; Original ; Original Article ; p53 Protein ; Parasitic diseases ; Pharmacology ; Promastigotes ; quantitative polymerase chain reaction ; reverse transcriptase polymerase chain reaction ; Stem Cells ; therapeutics ; Toxicity ; Usnic acid</subject><ispartof>3 Biotech, 2018-09, Vol.8 (9), p.384-7, Article 384</ispartof><rights>Springer-Verlag GmbH Germany, part of Springer Nature 2018</rights><rights>3 Biotech is a copyright of Springer, (2018). All Rights Reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c503t-a5a2d6cd1d7407c4aa30121ee5cbb5f097a6c22a2917cd1fc5fc6bd44f6bc3a03</citedby><cites>FETCH-LOGICAL-c503t-a5a2d6cd1d7407c4aa30121ee5cbb5f097a6c22a2917cd1fc5fc6bd44f6bc3a03</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6107478/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6107478/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,723,776,780,881,27903,27904,41467,42536,51297,53769,53771</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30148034$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Derici, Mehmet Kürşat</creatorcontrib><creatorcontrib>Cansaran-Duman, Demet</creatorcontrib><creatorcontrib>Taylan-Özkan, Ayşegül</creatorcontrib><title>Usnic acid causes apoptotic-like death in Leishmania major, L. infantum and L. tropica</title><title>3 Biotech</title><addtitle>3 Biotech</addtitle><addtitle>3 Biotech</addtitle><description>Leishmaniasis, a deadly parasitic infection, threatens many people worldwide. Since the high cost, toxicity, and resistance are drawbacks of current treatment options, it is necessary to find safer and more effective new antileishmanial drugs. The aim of this study was to determine the antileishmanial activity of usnic acid and its apoptotic mechanism on Leishmania spp. promastigotes. The antileishmanial activity was evaluated by MTT assay and apoptosis-related gene expression was investigated by qRT-PCR. Usnic acid was to be effective against Leishmania major, L. infantum , and L. tropica promastigotes at IC 50 = 10.76 µg/ml, 13.34 µg/ml, and 21.06 µg/ml, respectively. We also demonstrated a novel mechanism by which usnic acid inhibited proliferation and caused apoptosis; usnic acid upregulated p53, Bax, Casp-3 , and Casp-9 gene expression and downregulated the level of Bcl-2 gene expression. Accordingly, the expression level of the P53 gene increased in L. major, L. infantum and L. tropica by 14.4-, 11.8-, and 9.5-fold, respectively, and in contrast, the Bcl-2 gene expression decreased in all three leishmaniasis by 0.8-, 0.8-, and 0.7-fold, respectively. The present study, therefore, revealed that usnic acid played a critical role in the usnic acid-induced apoptotic process in Leishmania species. Usnic acid is easily accessible and an inexpensive agent, and can be considered as an alternative therapeutic agent for Leishmania infections subject to further tests in animal models.</description><subject>Acids</subject><subject>Agriculture</subject><subject>Animal models</subject><subject>antileishmanial properties</subject><subject>antileishmanials</subject><subject>Apoptosis</subject><subject>Bcl-2 protein</subject><subject>Bioinformatics</subject><subject>Biomaterials</subject><subject>Biotechnology</subject><subject>Cancer Research</subject><subject>Chemical compounds</subject><subject>Chemistry</subject><subject>Chemistry and Materials Science</subject><subject>death</subject><subject>Gene expression</subject><subject>gene expression regulation</subject><subject>genes</subject><subject>inhibitory concentration 50</subject><subject>Leishmania</subject><subject>Leishmania major</subject><subject>Leishmaniasis</subject><subject>Original</subject><subject>Original Article</subject><subject>p53 Protein</subject><subject>Parasitic diseases</subject><subject>Pharmacology</subject><subject>Promastigotes</subject><subject>quantitative polymerase chain reaction</subject><subject>reverse transcriptase polymerase chain reaction</subject><subject>Stem Cells</subject><subject>therapeutics</subject><subject>Toxicity</subject><subject>Usnic acid</subject><issn>2190-572X</issn><issn>2190-5738</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNp1kU1r3DAQhkVpaEKSH9BLMfTSQ51o9GlfCiWkH7CQS1N6E2NZzmprS65kF_rvq2XT7QdUl5Fmnnk1w0vIc6BXQKm-zsAZlTWFpgZB21o9IWcMWlpLzZunxzv7ckouc97RciTIFugzcsopiIZycUY-3-fgbYXW95XFNbtc4RznJS7e1qP_6qre4bKtfKg2zufthMFjNeEuptfV5qrkBwzLOlUY-v17SXH2Fi_IyYBjdpeP8Zzcv7v9dPOh3ty9_3jzdlNbSflSo0TWK9tDrwXVViCWyRg4J23XyYG2GpVlDFkLulCDlYNVXS_EoDrLkfJz8uagO6_d5HrrwpJwNHPyE6YfJqI3f1eC35qH-N0ooFropgi8ehRI8dvq8mImn60bRwwurtkwANVCKzgr6Mt_0F1cUyjrGUZbxhsBShcKDpRNMefkhuMwQM3eOHMwzhTjzN44o0rPiz-3OHb8sqkA7ADkUgoPLv3--v-qPwFz_KNN</recordid><startdate>20180901</startdate><enddate>20180901</enddate><creator>Derici, Mehmet Kürşat</creator><creator>Cansaran-Duman, Demet</creator><creator>Taylan-Özkan, Ayşegül</creator><general>Springer International Publishing</general><general>Springer Nature B.V</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>8AO</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>ABJCF</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>L6V</scope><scope>LK8</scope><scope>M7P</scope><scope>M7S</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>7S9</scope><scope>L.6</scope><scope>5PM</scope></search><sort><creationdate>20180901</creationdate><title>Usnic acid causes apoptotic-like death in Leishmania major, L. infantum and L. tropica</title><author>Derici, Mehmet Kürşat ; Cansaran-Duman, Demet ; Taylan-Özkan, Ayşegül</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c503t-a5a2d6cd1d7407c4aa30121ee5cbb5f097a6c22a2917cd1fc5fc6bd44f6bc3a03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Acids</topic><topic>Agriculture</topic><topic>Animal models</topic><topic>antileishmanial properties</topic><topic>antileishmanials</topic><topic>Apoptosis</topic><topic>Bcl-2 protein</topic><topic>Bioinformatics</topic><topic>Biomaterials</topic><topic>Biotechnology</topic><topic>Cancer Research</topic><topic>Chemical compounds</topic><topic>Chemistry</topic><topic>Chemistry and Materials Science</topic><topic>death</topic><topic>Gene expression</topic><topic>gene expression regulation</topic><topic>genes</topic><topic>inhibitory concentration 50</topic><topic>Leishmania</topic><topic>Leishmania major</topic><topic>Leishmaniasis</topic><topic>Original</topic><topic>Original Article</topic><topic>p53 Protein</topic><topic>Parasitic diseases</topic><topic>Pharmacology</topic><topic>Promastigotes</topic><topic>quantitative polymerase chain reaction</topic><topic>reverse transcriptase polymerase chain reaction</topic><topic>Stem Cells</topic><topic>therapeutics</topic><topic>Toxicity</topic><topic>Usnic acid</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Derici, Mehmet Kürşat</creatorcontrib><creatorcontrib>Cansaran-Duman, Demet</creatorcontrib><creatorcontrib>Taylan-Özkan, Ayşegül</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Pharma Collection</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection (ProQuest)</collection><collection>Natural Science Collection (ProQuest)</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Engineering Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Engineering Collection</collection><collection>AGRICOLA</collection><collection>AGRICOLA - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>3 Biotech</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Derici, Mehmet Kürşat</au><au>Cansaran-Duman, Demet</au><au>Taylan-Özkan, Ayşegül</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Usnic acid causes apoptotic-like death in Leishmania major, L. infantum and L. tropica</atitle><jtitle>3 Biotech</jtitle><stitle>3 Biotech</stitle><addtitle>3 Biotech</addtitle><date>2018-09-01</date><risdate>2018</risdate><volume>8</volume><issue>9</issue><spage>384</spage><epage>7</epage><pages>384-7</pages><artnum>384</artnum><issn>2190-572X</issn><eissn>2190-5738</eissn><abstract>Leishmaniasis, a deadly parasitic infection, threatens many people worldwide. Since the high cost, toxicity, and resistance are drawbacks of current treatment options, it is necessary to find safer and more effective new antileishmanial drugs. The aim of this study was to determine the antileishmanial activity of usnic acid and its apoptotic mechanism on Leishmania spp. promastigotes. The antileishmanial activity was evaluated by MTT assay and apoptosis-related gene expression was investigated by qRT-PCR. Usnic acid was to be effective against Leishmania major, L. infantum , and L. tropica promastigotes at IC 50 = 10.76 µg/ml, 13.34 µg/ml, and 21.06 µg/ml, respectively. We also demonstrated a novel mechanism by which usnic acid inhibited proliferation and caused apoptosis; usnic acid upregulated p53, Bax, Casp-3 , and Casp-9 gene expression and downregulated the level of Bcl-2 gene expression. Accordingly, the expression level of the P53 gene increased in L. major, L. infantum and L. tropica by 14.4-, 11.8-, and 9.5-fold, respectively, and in contrast, the Bcl-2 gene expression decreased in all three leishmaniasis by 0.8-, 0.8-, and 0.7-fold, respectively. The present study, therefore, revealed that usnic acid played a critical role in the usnic acid-induced apoptotic process in Leishmania species. Usnic acid is easily accessible and an inexpensive agent, and can be considered as an alternative therapeutic agent for Leishmania infections subject to further tests in animal models.</abstract><cop>Cham</cop><pub>Springer International Publishing</pub><pmid>30148034</pmid><doi>10.1007/s13205-018-1409-6</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record>
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subjects	Acids Agriculture Animal models antileishmanial properties antileishmanials Apoptosis Bcl-2 protein Bioinformatics Biomaterials Biotechnology Cancer Research Chemical compounds Chemistry Chemistry and Materials Science death Gene expression gene expression regulation genes inhibitory concentration 50 Leishmania Leishmania major Leishmaniasis Original Original Article p53 Protein Parasitic diseases Pharmacology Promastigotes quantitative polymerase chain reaction reverse transcriptase polymerase chain reaction Stem Cells therapeutics Toxicity Usnic acid
title	Usnic acid causes apoptotic-like death in Leishmania major, L. infantum and L. tropica
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