Investigation of a new oxazolidine derivative in human resistance acute leukemia cells: deciphering its mechanism of action by label-free proteomic
The present study aimed to evaluate the mechanism of action of the antineoplastic activity of an oxazolidine derivative, LPSF/NB-3 (5-(4-cloro-benzilideno)-3-etil-2-tioxo-oxazolidin-4-ona). Cytotoxicity assays were performed in peripheral blood mononuclear cells (PBMCs) and resistant acute leukemia...
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| creator | do Nascimento Carvalho, Lidiane Vasconcelos de Sena, Wanessa Layssa Batista Abdelhay, Eliana Pereira, Michelly Cristiny da Rocha Pitta, Maira Galdino do Carmo Alves de Lima, Maria Souza, Gustavo Henrique Martins Ferreira Pizzatti, Luciana da Rocha Pitta, Ivan de Melo Rêgo, Moacyr Jesus Barreto |
| description | The present study aimed to evaluate the mechanism of action of the antineoplastic activity of an oxazolidine derivative, LPSF/NB-3 (5-(4-cloro-benzilideno)-3-etil-2-tioxo-oxazolidin-4-ona). Cytotoxicity assays were performed in peripheral blood mononuclear cells (PBMCs) and resistant acute leukemia cell line (HL-60/MX1) by the MTT method. LPSF/NB-3 exhibited cytotoxicity in HL-60/MX1, but it was not toxic to healthy cells in the highest dose tested (100 μM). The protein extract of HL-60/MX1 cells treated with LPSF/NB-3 was subjected to proteomic analysis using two-dimensional chromatography coupled to mass spectrometry. We could identify a total of 2652 proteins, in which 633 were statistically modulated. Within the group of protein considered for the quantitative analysis with the established criteria, 262 were differentially expressed, 146 with increased expression and 116 with decreased expression in the sample treated with LPSF/NB-3 compared to the control. The following differentially expressed pathways were found: involving regulation of the cytoskeleton, DNA damage, and transduce cellular signals. Networks that were highlighted are related to the immune system. The ELISA technique was used to assess the immunomodulatory potential of LPSF/NB-3 in PBMCs. We observed significant decrease of IFNγ (
p
< 0.01) and dose-response pattern of the cytokines IL-6, IL-17A, IL-22, and IL-10. Therefore, results suggest that LPSF/NB-3 appears to modulate important pathways, including cell cycle and immune system regulatory pathways. |
| doi_str_mv | 10.1007/s00210-020-02024-8 |
| format | Article |
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p
< 0.01) and dose-response pattern of the cytokines IL-6, IL-17A, IL-22, and IL-10. Therefore, results suggest that LPSF/NB-3 appears to modulate important pathways, including cell cycle and immune system regulatory pathways.</description><identifier>ISSN: 0028-1298</identifier><identifier>EISSN: 1432-1912</identifier><identifier>DOI: 10.1007/s00210-020-02024-8</identifier><identifier>PMID: 33475759</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer Berlin Heidelberg</publisher><subject>Antineoplastic Agents - administration & dosage ; Antineoplastic Agents - pharmacology ; Biomedical and Life Sciences ; Biomedicine ; Cell cycle ; Cell Cycle - drug effects ; Cytokines - metabolism ; Cytoskeleton ; Cytotoxicity ; DNA damage ; Dose-Response Relationship, Drug ; Drug Resistance, Neoplasm ; Enzyme-linked immunosorbent assay ; HL-60 Cells ; Humans ; Immune system ; Immunomodulation ; Interleukin 10 ; Interleukin 22 ; Interleukin 6 ; Leukemia ; Leukemia, Promyelocytic, Acute - drug therapy ; Leukemia, Promyelocytic, Acute - pathology ; Leukocytes (mononuclear) ; Leukocytes, Mononuclear - drug effects ; Mass spectroscopy ; Neurosciences ; Original Article ; Oxazoles - administration & dosage ; Oxazoles - chemistry ; Oxazoles - pharmacology ; Peripheral blood mononuclear cells ; Pharmacology/Toxicology ; Proteomics - methods ; Signal Transduction - drug effects ; γ-Interferon</subject><ispartof>Naunyn-Schmiedeberg's archives of pharmacology, 2021-06, Vol.394 (6), p.1153-1166</ispartof><rights>Springer-Verlag GmbH Germany, part of Springer Nature 2021</rights><rights>Springer-Verlag GmbH Germany, part of Springer Nature 2021.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c326t-e1dc90e9de1e6da779c40bf236437ac204ff678e32b18297b4ed91256970b9633</cites><orcidid>0000-0002-1883-6012</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s00210-020-02024-8$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00210-020-02024-8$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,780,784,27924,27925,41488,42557,51319</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33475759$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>do Nascimento Carvalho, Lidiane Vasconcelos</creatorcontrib><creatorcontrib>de Sena, Wanessa Layssa Batista</creatorcontrib><creatorcontrib>Abdelhay, Eliana</creatorcontrib><creatorcontrib>Pereira, Michelly Cristiny</creatorcontrib><creatorcontrib>da Rocha Pitta, Maira Galdino</creatorcontrib><creatorcontrib>do Carmo Alves de Lima, Maria</creatorcontrib><creatorcontrib>Souza, Gustavo Henrique Martins Ferreira</creatorcontrib><creatorcontrib>Pizzatti, Luciana</creatorcontrib><creatorcontrib>da Rocha Pitta, Ivan</creatorcontrib><creatorcontrib>de Melo Rêgo, Moacyr Jesus Barreto</creatorcontrib><title>Investigation of a new oxazolidine derivative in human resistance acute leukemia cells: deciphering its mechanism of action by label-free proteomic</title><title>Naunyn-Schmiedeberg's archives of pharmacology</title><addtitle>Naunyn-Schmiedeberg's Arch Pharmacol</addtitle><addtitle>Naunyn Schmiedebergs Arch Pharmacol</addtitle><description>The present study aimed to evaluate the mechanism of action of the antineoplastic activity of an oxazolidine derivative, LPSF/NB-3 (5-(4-cloro-benzilideno)-3-etil-2-tioxo-oxazolidin-4-ona). Cytotoxicity assays were performed in peripheral blood mononuclear cells (PBMCs) and resistant acute leukemia cell line (HL-60/MX1) by the MTT method. LPSF/NB-3 exhibited cytotoxicity in HL-60/MX1, but it was not toxic to healthy cells in the highest dose tested (100 μM). The protein extract of HL-60/MX1 cells treated with LPSF/NB-3 was subjected to proteomic analysis using two-dimensional chromatography coupled to mass spectrometry. We could identify a total of 2652 proteins, in which 633 were statistically modulated. Within the group of protein considered for the quantitative analysis with the established criteria, 262 were differentially expressed, 146 with increased expression and 116 with decreased expression in the sample treated with LPSF/NB-3 compared to the control. The following differentially expressed pathways were found: involving regulation of the cytoskeleton, DNA damage, and transduce cellular signals. Networks that were highlighted are related to the immune system. The ELISA technique was used to assess the immunomodulatory potential of LPSF/NB-3 in PBMCs. We observed significant decrease of IFNγ (
p
< 0.01) and dose-response pattern of the cytokines IL-6, IL-17A, IL-22, and IL-10. Therefore, results suggest that LPSF/NB-3 appears to modulate important pathways, including cell cycle and immune system regulatory pathways.</description><subject>Antineoplastic Agents - administration & dosage</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Cell cycle</subject><subject>Cell Cycle - drug effects</subject><subject>Cytokines - metabolism</subject><subject>Cytoskeleton</subject><subject>Cytotoxicity</subject><subject>DNA damage</subject><subject>Dose-Response Relationship, Drug</subject><subject>Drug Resistance, Neoplasm</subject><subject>Enzyme-linked immunosorbent assay</subject><subject>HL-60 Cells</subject><subject>Humans</subject><subject>Immune system</subject><subject>Immunomodulation</subject><subject>Interleukin 10</subject><subject>Interleukin 22</subject><subject>Interleukin 6</subject><subject>Leukemia</subject><subject>Leukemia, Promyelocytic, Acute - drug therapy</subject><subject>Leukemia, Promyelocytic, Acute - pathology</subject><subject>Leukocytes (mononuclear)</subject><subject>Leukocytes, Mononuclear - drug effects</subject><subject>Mass spectroscopy</subject><subject>Neurosciences</subject><subject>Original Article</subject><subject>Oxazoles - administration & dosage</subject><subject>Oxazoles - chemistry</subject><subject>Oxazoles - pharmacology</subject><subject>Peripheral blood mononuclear cells</subject><subject>Pharmacology/Toxicology</subject><subject>Proteomics - methods</subject><subject>Signal Transduction - drug effects</subject><subject>γ-Interferon</subject><issn>0028-1298</issn><issn>1432-1912</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNp9kclOwzAURS0EglL4ARbIEuuAhySO2aGKSUJiA2vLcV5al8QpdlKG3-CHcQdgx8Ly4t1BOhehE0rOKSHiIhDCKEkIWz-WJsUOGtGUs4RKynbRKN6LhDJZHKDDEOaEkJxm2T464DwVmcjkCH3duyWE3k51bzuHuxpr7OANd-_6s2tsZR3gCrxdxvsSsHV4NrTaYQ_Bhl47A1iboQfcwPACrdXYQNOEy2gydjGLTjfFtg-4BTPTzoZ23WHWbeUHbnQJTVJ7ALzwXQ9da80R2qt1E-B4-4_R88310-QueXi8vZ9cPSSGs7xPgFZGEpAVUMgrLYQ0KSlrxvOUC20YSes6FwVwVtKCSVGmUEUuWS4FKWXO-RidbXJj8-sQKah5N3gXKxXL0kgqI4WIKrZRGd-F4KFWC29b7T8UJWq1g9rsoOIGar2DKqLpdBs9lC1Uv5Yf8FHAN4KwWCEC_9f9T-w3EgyVZw</recordid><startdate>20210601</startdate><enddate>20210601</enddate><creator>do Nascimento Carvalho, Lidiane Vasconcelos</creator><creator>de Sena, Wanessa Layssa Batista</creator><creator>Abdelhay, Eliana</creator><creator>Pereira, Michelly Cristiny</creator><creator>da Rocha Pitta, Maira Galdino</creator><creator>do Carmo Alves de Lima, Maria</creator><creator>Souza, Gustavo Henrique Martins Ferreira</creator><creator>Pizzatti, Luciana</creator><creator>da Rocha Pitta, Ivan</creator><creator>de Melo Rêgo, Moacyr Jesus Barreto</creator><general>Springer Berlin Heidelberg</general><general>Springer Nature B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QP</scope><scope>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><orcidid>https://orcid.org/0000-0002-1883-6012</orcidid></search><sort><creationdate>20210601</creationdate><title>Investigation of a new oxazolidine derivative in human resistance acute leukemia cells: deciphering its mechanism of action by label-free proteomic</title><author>do Nascimento Carvalho, Lidiane Vasconcelos ; de Sena, Wanessa Layssa Batista ; Abdelhay, Eliana ; Pereira, Michelly Cristiny ; da Rocha Pitta, Maira Galdino ; do Carmo Alves de Lima, Maria ; Souza, Gustavo Henrique Martins Ferreira ; Pizzatti, Luciana ; da Rocha Pitta, Ivan ; de Melo Rêgo, Moacyr Jesus Barreto</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c326t-e1dc90e9de1e6da779c40bf236437ac204ff678e32b18297b4ed91256970b9633</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Antineoplastic Agents - administration & dosage</topic><topic>Antineoplastic Agents - pharmacology</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Cell cycle</topic><topic>Cell Cycle - drug effects</topic><topic>Cytokines - metabolism</topic><topic>Cytoskeleton</topic><topic>Cytotoxicity</topic><topic>DNA damage</topic><topic>Dose-Response Relationship, Drug</topic><topic>Drug Resistance, Neoplasm</topic><topic>Enzyme-linked immunosorbent assay</topic><topic>HL-60 Cells</topic><topic>Humans</topic><topic>Immune system</topic><topic>Immunomodulation</topic><topic>Interleukin 10</topic><topic>Interleukin 22</topic><topic>Interleukin 6</topic><topic>Leukemia</topic><topic>Leukemia, Promyelocytic, Acute - drug therapy</topic><topic>Leukemia, Promyelocytic, Acute - pathology</topic><topic>Leukocytes (mononuclear)</topic><topic>Leukocytes, Mononuclear - drug effects</topic><topic>Mass spectroscopy</topic><topic>Neurosciences</topic><topic>Original Article</topic><topic>Oxazoles - administration & dosage</topic><topic>Oxazoles - chemistry</topic><topic>Oxazoles - pharmacology</topic><topic>Peripheral blood mononuclear cells</topic><topic>Pharmacology/Toxicology</topic><topic>Proteomics - methods</topic><topic>Signal Transduction - drug effects</topic><topic>γ-Interferon</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>do Nascimento Carvalho, Lidiane Vasconcelos</creatorcontrib><creatorcontrib>de Sena, Wanessa Layssa Batista</creatorcontrib><creatorcontrib>Abdelhay, Eliana</creatorcontrib><creatorcontrib>Pereira, Michelly Cristiny</creatorcontrib><creatorcontrib>da Rocha Pitta, Maira Galdino</creatorcontrib><creatorcontrib>do Carmo Alves de Lima, Maria</creatorcontrib><creatorcontrib>Souza, Gustavo Henrique Martins Ferreira</creatorcontrib><creatorcontrib>Pizzatti, Luciana</creatorcontrib><creatorcontrib>da Rocha Pitta, Ivan</creatorcontrib><creatorcontrib>de Melo Rêgo, Moacyr Jesus Barreto</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical 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><jtitle>Naunyn-Schmiedeberg's archives of pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>do Nascimento Carvalho, Lidiane Vasconcelos</au><au>de Sena, Wanessa Layssa Batista</au><au>Abdelhay, Eliana</au><au>Pereira, Michelly Cristiny</au><au>da Rocha Pitta, Maira Galdino</au><au>do Carmo Alves de Lima, Maria</au><au>Souza, Gustavo Henrique Martins Ferreira</au><au>Pizzatti, Luciana</au><au>da Rocha Pitta, Ivan</au><au>de Melo Rêgo, Moacyr Jesus Barreto</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Investigation of a new oxazolidine derivative in human resistance acute leukemia cells: deciphering its mechanism of action by label-free proteomic</atitle><jtitle>Naunyn-Schmiedeberg's archives of pharmacology</jtitle><stitle>Naunyn-Schmiedeberg's Arch Pharmacol</stitle><addtitle>Naunyn Schmiedebergs Arch Pharmacol</addtitle><date>2021-06-01</date><risdate>2021</risdate><volume>394</volume><issue>6</issue><spage>1153</spage><epage>1166</epage><pages>1153-1166</pages><issn>0028-1298</issn><eissn>1432-1912</eissn><abstract>The present study aimed to evaluate the mechanism of action of the antineoplastic activity of an oxazolidine derivative, LPSF/NB-3 (5-(4-cloro-benzilideno)-3-etil-2-tioxo-oxazolidin-4-ona). Cytotoxicity assays were performed in peripheral blood mononuclear cells (PBMCs) and resistant acute leukemia cell line (HL-60/MX1) by the MTT method. LPSF/NB-3 exhibited cytotoxicity in HL-60/MX1, but it was not toxic to healthy cells in the highest dose tested (100 μM). The protein extract of HL-60/MX1 cells treated with LPSF/NB-3 was subjected to proteomic analysis using two-dimensional chromatography coupled to mass spectrometry. We could identify a total of 2652 proteins, in which 633 were statistically modulated. Within the group of protein considered for the quantitative analysis with the established criteria, 262 were differentially expressed, 146 with increased expression and 116 with decreased expression in the sample treated with LPSF/NB-3 compared to the control. The following differentially expressed pathways were found: involving regulation of the cytoskeleton, DNA damage, and transduce cellular signals. Networks that were highlighted are related to the immune system. The ELISA technique was used to assess the immunomodulatory potential of LPSF/NB-3 in PBMCs. We observed significant decrease of IFNγ (
p
< 0.01) and dose-response pattern of the cytokines IL-6, IL-17A, IL-22, and IL-10. Therefore, results suggest that LPSF/NB-3 appears to modulate important pathways, including cell cycle and immune system regulatory pathways.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer Berlin Heidelberg</pub><pmid>33475759</pmid><doi>10.1007/s00210-020-02024-8</doi><tpages>14</tpages><orcidid>https://orcid.org/0000-0002-1883-6012</orcidid></addata></record> |
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| issn | 0028-1298 1432-1912 |
| language | eng |
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| source | MEDLINE; SpringerLink Journals - AutoHoldings |
| subjects | Antineoplastic Agents - administration & dosage Antineoplastic Agents - pharmacology Biomedical and Life Sciences Biomedicine Cell cycle Cell Cycle - drug effects Cytokines - metabolism Cytoskeleton Cytotoxicity DNA damage Dose-Response Relationship, Drug Drug Resistance, Neoplasm Enzyme-linked immunosorbent assay HL-60 Cells Humans Immune system Immunomodulation Interleukin 10 Interleukin 22 Interleukin 6 Leukemia Leukemia, Promyelocytic, Acute - drug therapy Leukemia, Promyelocytic, Acute - pathology Leukocytes (mononuclear) Leukocytes, Mononuclear - drug effects Mass spectroscopy Neurosciences Original Article Oxazoles - administration & dosage Oxazoles - chemistry Oxazoles - pharmacology Peripheral blood mononuclear cells Pharmacology/Toxicology Proteomics - methods Signal Transduction - drug effects γ-Interferon |
| title | Investigation of a new oxazolidine derivative in human resistance acute leukemia cells: deciphering its mechanism of action by label-free proteomic |
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