CR-LAAO, an L-amino acid oxidase from Calloselasma rhodostoma venom, as a potential tool for developing novel immunotherapeutic strategies against cancer
L-amino acid oxidases from snake venoms have been described to possess various biological functions. In this study, we investigated the inflammatory responses induced in vivo and in vitro by CR-LAAO, an L-amino acid oxidase isolated from Calloselasma rhodostoma venom, and its antitumor potential. CR...
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| Veröffentlicht in: | Scientific reports 2017-02, Vol.7 (1), p.42673, Article 42673 |
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| creator | Costa, Tássia R. Menaldo, Danilo L. Zoccal, Karina F. Burin, Sandra M. Aissa, Alexandre F. Castro, Fabíola A. de Faccioli, Lúcia H. Greggi Antunes, Lusânia M. Sampaio, Suely V. |
| description | L-amino acid oxidases from snake venoms have been described to possess various biological functions. In this study, we investigated the inflammatory responses induced
in vivo
and
in vitro
by CR-LAAO, an L-amino acid oxidase isolated from
Calloselasma rhodostoma
venom, and its antitumor potential. CR-LAAO induced acute inflammatory responses
in vivo
, with recruitment of neutrophils and release of IL-6, IL-1β, LTB
4
and PGE
2
.
In vitro
, IL-6 and IL-1β production by peritoneal macrophages stimulated with CR-LAAO was dependent of the activation of the Toll-like receptors TLR2 and TLR4. In addition, CR-LAAO promoted apoptosis of HL-60 and HepG2 tumor cells mediated by the release of hydrogen peroxide and activation of immune cells, resulting in oxidative stress and production of IL-6 and IL-1β that triggered a series of events, such as activation of caspase 8, 9 and 3, and the expression of the pro-apoptotic gene
BAX
. We also observed that CR-LAAO modulated the cell cycle of these tumor cells, promoting delay in the G0/G1 and S phases. Taken together, our results suggest that CR-LAAO could serve as a potential tool for the development of novel immunotherapeutic strategies against cancer, since this toxin promoted apoptosis of tumor cells and also activated immune cells against them. |
| doi_str_mv | 10.1038/srep42673 |
| format | Article |
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in vivo
and
in vitro
by CR-LAAO, an L-amino acid oxidase isolated from
Calloselasma rhodostoma
venom, and its antitumor potential. CR-LAAO induced acute inflammatory responses
in vivo
, with recruitment of neutrophils and release of IL-6, IL-1β, LTB
4
and PGE
2
.
In vitro
, IL-6 and IL-1β production by peritoneal macrophages stimulated with CR-LAAO was dependent of the activation of the Toll-like receptors TLR2 and TLR4. In addition, CR-LAAO promoted apoptosis of HL-60 and HepG2 tumor cells mediated by the release of hydrogen peroxide and activation of immune cells, resulting in oxidative stress and production of IL-6 and IL-1β that triggered a series of events, such as activation of caspase 8, 9 and 3, and the expression of the pro-apoptotic gene
BAX
. We also observed that CR-LAAO modulated the cell cycle of these tumor cells, promoting delay in the G0/G1 and S phases. Taken together, our results suggest that CR-LAAO could serve as a potential tool for the development of novel immunotherapeutic strategies against cancer, since this toxin promoted apoptosis of tumor cells and also activated immune cells against them.</description><identifier>ISSN: 2045-2322</identifier><identifier>EISSN: 2045-2322</identifier><identifier>DOI: 10.1038/srep42673</identifier><identifier>PMID: 28205610</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>13/2 ; 13/31 ; 38/77 ; 38/90 ; 631/250/256/2516 ; 631/67/580 ; 82/80 ; Amino acid oxidase ; Amino acids ; Apoptosis ; Cancer ; Caspase ; Caspase-8 ; Cell activation ; Cell cycle ; Humanities and Social Sciences ; Hydrogen peroxide ; Inflammation ; Interleukin 6 ; Leukocytes (neutrophilic) ; Macrophages ; multidisciplinary ; Oxidative stress ; Peritoneum ; Prostaglandin E2 ; Science ; TLR2 protein ; TLR4 protein ; Toll-like receptors ; Toxins ; Tumor cells ; Venom</subject><ispartof>Scientific reports, 2017-02, Vol.7 (1), p.42673, Article 42673</ispartof><rights>The Author(s) 2017</rights><rights>Copyright Nature Publishing Group Feb 2017</rights><rights>Copyright © 2017, The Author(s) 2017 The Author(s)</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c504t-e1f7f7a116b776386c456e67b5aaa6480ad4d84c75c9c70bb309a026e1a77e313</citedby><cites>FETCH-LOGICAL-c504t-e1f7f7a116b776386c456e67b5aaa6480ad4d84c75c9c70bb309a026e1a77e313</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/PMC5311993/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5311993/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,27901,27902,41096,42165,51551,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28205610$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Costa, Tássia R.</creatorcontrib><creatorcontrib>Menaldo, Danilo L.</creatorcontrib><creatorcontrib>Zoccal, Karina F.</creatorcontrib><creatorcontrib>Burin, Sandra M.</creatorcontrib><creatorcontrib>Aissa, Alexandre F.</creatorcontrib><creatorcontrib>Castro, Fabíola A. de</creatorcontrib><creatorcontrib>Faccioli, Lúcia H.</creatorcontrib><creatorcontrib>Greggi Antunes, Lusânia M.</creatorcontrib><creatorcontrib>Sampaio, Suely V.</creatorcontrib><title>CR-LAAO, an L-amino acid oxidase from Calloselasma rhodostoma venom, as a potential tool for developing novel immunotherapeutic strategies against cancer</title><title>Scientific reports</title><addtitle>Sci Rep</addtitle><addtitle>Sci Rep</addtitle><description>L-amino acid oxidases from snake venoms have been described to possess various biological functions. In this study, we investigated the inflammatory responses induced
in vivo
and
in vitro
by CR-LAAO, an L-amino acid oxidase isolated from
Calloselasma rhodostoma
venom, and its antitumor potential. CR-LAAO induced acute inflammatory responses
in vivo
, with recruitment of neutrophils and release of IL-6, IL-1β, LTB
4
and PGE
2
.
In vitro
, IL-6 and IL-1β production by peritoneal macrophages stimulated with CR-LAAO was dependent of the activation of the Toll-like receptors TLR2 and TLR4. In addition, CR-LAAO promoted apoptosis of HL-60 and HepG2 tumor cells mediated by the release of hydrogen peroxide and activation of immune cells, resulting in oxidative stress and production of IL-6 and IL-1β that triggered a series of events, such as activation of caspase 8, 9 and 3, and the expression of the pro-apoptotic gene
BAX
. We also observed that CR-LAAO modulated the cell cycle of these tumor cells, promoting delay in the G0/G1 and S phases. Taken together, our results suggest that CR-LAAO could serve as a potential tool for the development of novel immunotherapeutic strategies against cancer, since this toxin promoted apoptosis of tumor cells and also activated immune cells against them.</description><subject>13/2</subject><subject>13/31</subject><subject>38/77</subject><subject>38/90</subject><subject>631/250/256/2516</subject><subject>631/67/580</subject><subject>82/80</subject><subject>Amino acid oxidase</subject><subject>Amino acids</subject><subject>Apoptosis</subject><subject>Cancer</subject><subject>Caspase</subject><subject>Caspase-8</subject><subject>Cell activation</subject><subject>Cell cycle</subject><subject>Humanities and Social Sciences</subject><subject>Hydrogen peroxide</subject><subject>Inflammation</subject><subject>Interleukin 6</subject><subject>Leukocytes (neutrophilic)</subject><subject>Macrophages</subject><subject>multidisciplinary</subject><subject>Oxidative stress</subject><subject>Peritoneum</subject><subject>Prostaglandin E2</subject><subject>Science</subject><subject>TLR2 protein</subject><subject>TLR4 protein</subject><subject>Toll-like receptors</subject><subject>Toxins</subject><subject>Tumor cells</subject><subject>Venom</subject><issn>2045-2322</issn><issn>2045-2322</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>BENPR</sourceid><recordid>eNplkV-L1DAUxYso7rLug19AAj4pW02atmlfhGHwHwwsiD6H2_S2k6XNrUk67H4Uv62RWYcR85ID95dzTzhZ9lLwd4LL5n3wuJRFreST7LLgZZUXsiienumL7DqEO55OVbSlaJ9nF0VT8KoW_DL7tf2W7zab2xsGju1ymK0jBsb2jO5tDwHZ4GlmW5gmCjhBmIH5PfUUIiV5QEdzehsYsIUiumhhYpFoYgN51uMBJ1qsG5mjJJmd59VR3KOHBddoDQvRQ8TRYrIYwboQmQFn0L_Ing0wBbx-vK-yH58-ft9-yXe3n79uN7vcVLyMOYpBDQqEqDulatnUpqxqrFVXAUBdNhz6sm9KoyrTGsW7TvIWeFGjAKVQCnmVfTj6Lms3Y2_SHzxMevF2Bv-gCaz-d-LsXo900JUUom1lMnj9aODp54oh6jtavUuZtWi5UCLlVIl6c6SMp5A6G04bBNd_itSnIhP76jzSifxbWwLeHoGQRm5Ef7byP7ffawyqbA</recordid><startdate>20170216</startdate><enddate>20170216</enddate><creator>Costa, Tássia R.</creator><creator>Menaldo, Danilo L.</creator><creator>Zoccal, Karina F.</creator><creator>Burin, Sandra M.</creator><creator>Aissa, 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cancer</title><author>Costa, Tássia R. ; Menaldo, Danilo L. ; Zoccal, Karina F. ; Burin, Sandra M. ; Aissa, Alexandre F. ; Castro, Fabíola A. de ; Faccioli, Lúcia H. ; Greggi Antunes, Lusânia M. ; Sampaio, Suely V.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c504t-e1f7f7a116b776386c456e67b5aaa6480ad4d84c75c9c70bb309a026e1a77e313</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>13/2</topic><topic>13/31</topic><topic>38/77</topic><topic>38/90</topic><topic>631/250/256/2516</topic><topic>631/67/580</topic><topic>82/80</topic><topic>Amino acid oxidase</topic><topic>Amino acids</topic><topic>Apoptosis</topic><topic>Cancer</topic><topic>Caspase</topic><topic>Caspase-8</topic><topic>Cell activation</topic><topic>Cell cycle</topic><topic>Humanities and Social Sciences</topic><topic>Hydrogen peroxide</topic><topic>Inflammation</topic><topic>Interleukin 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Edition</collection><collection>ProQuest Central Basic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Scientific reports</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Costa, Tássia R.</au><au>Menaldo, Danilo L.</au><au>Zoccal, Karina F.</au><au>Burin, Sandra M.</au><au>Aissa, Alexandre F.</au><au>Castro, Fabíola A. de</au><au>Faccioli, Lúcia H.</au><au>Greggi Antunes, Lusânia M.</au><au>Sampaio, Suely V.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>CR-LAAO, an L-amino acid oxidase from Calloselasma rhodostoma venom, as a potential tool for developing novel immunotherapeutic strategies against cancer</atitle><jtitle>Scientific reports</jtitle><stitle>Sci Rep</stitle><addtitle>Sci Rep</addtitle><date>2017-02-16</date><risdate>2017</risdate><volume>7</volume><issue>1</issue><spage>42673</spage><pages>42673-</pages><artnum>42673</artnum><issn>2045-2322</issn><eissn>2045-2322</eissn><abstract>L-amino acid oxidases from snake venoms have been described to possess various biological functions. In this study, we investigated the inflammatory responses induced
in vivo
and
in vitro
by CR-LAAO, an L-amino acid oxidase isolated from
Calloselasma rhodostoma
venom, and its antitumor potential. CR-LAAO induced acute inflammatory responses
in vivo
, with recruitment of neutrophils and release of IL-6, IL-1β, LTB
4
and PGE
2
.
In vitro
, IL-6 and IL-1β production by peritoneal macrophages stimulated with CR-LAAO was dependent of the activation of the Toll-like receptors TLR2 and TLR4. In addition, CR-LAAO promoted apoptosis of HL-60 and HepG2 tumor cells mediated by the release of hydrogen peroxide and activation of immune cells, resulting in oxidative stress and production of IL-6 and IL-1β that triggered a series of events, such as activation of caspase 8, 9 and 3, and the expression of the pro-apoptotic gene
BAX
. We also observed that CR-LAAO modulated the cell cycle of these tumor cells, promoting delay in the G0/G1 and S phases. Taken together, our results suggest that CR-LAAO could serve as a potential tool for the development of novel immunotherapeutic strategies against cancer, since this toxin promoted apoptosis of tumor cells and also activated immune cells against them.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>28205610</pmid><doi>10.1038/srep42673</doi><oa>free_for_read</oa></addata></record> |
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| subjects | 13/2 13/31 38/77 38/90 631/250/256/2516 631/67/580 82/80 Amino acid oxidase Amino acids Apoptosis Cancer Caspase Caspase-8 Cell activation Cell cycle Humanities and Social Sciences Hydrogen peroxide Inflammation Interleukin 6 Leukocytes (neutrophilic) Macrophages multidisciplinary Oxidative stress Peritoneum Prostaglandin E2 Science TLR2 protein TLR4 protein Toll-like receptors Toxins Tumor cells Venom |
| title | CR-LAAO, an L-amino acid oxidase from Calloselasma rhodostoma venom, as a potential tool for developing novel immunotherapeutic strategies against cancer |
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