Mechanisms underlying the antiproliferative effects of a series of quinoxaline-derived chalcones
Autor(a) principal: | |
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Data de Publicação: | 2017 |
Outros Autores: | , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UFRGS |
Texto Completo: | http://hdl.handle.net/10183/188813 |
Resumo: | The present study aimed to characterize the effects of quinoxaline-derived chalcones, designed on the basis of the selective PI3Kγ inhibitor AS605240, in oral cancer cells. Three lead compounds, namely N9, N17 and N23, were selected from a series of 20 quinoxaline-derived chalcones, based on an initial screening using human and rat squamous cell carcinoma lineages, representing compounds with at least one methoxy radical at the A-ring. The selected chalcones, mainly N9 and N17, displayed marked antiproliferative effects, via apoptosis and autophagy induction, with an increase of sub-G1 population and Akt inhibition. The three chalcones displayed marked in vitro antitumor effects in different protocols with standard chemotherapy drugs, with acceptable toxicity on normal cells. There was no growth retrieval, after exposure to chalcone N9 alone, in a long-term assay to determine the cumulative population doubling (CPD) of human oral cancer cells. A PCR array evaluating 168 genes related to cancer and inflammation, demonstrated striking actions for N9, which altered the expression of 74 genes. Altogether, our results point out quinoxalinic chalcones, mainly N9, as potential strategies for oral cancer treatment. |
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Mielcke, Tânia ReginaMuradás, Thaís CristinaChiela, Eduardo Cremonese FilippiAmaral, Maria Eduarda AzambujaKist, Luiza WilgesBogo, Mauricio ReisMascarello, AlessandraNeuenfeldt, Patrícia DevantierNunes, Ricardo JoséCampos, Maria Martha2019-02-15T02:33:45Z20172045-2322http://hdl.handle.net/10183/188813001087295The present study aimed to characterize the effects of quinoxaline-derived chalcones, designed on the basis of the selective PI3Kγ inhibitor AS605240, in oral cancer cells. Three lead compounds, namely N9, N17 and N23, were selected from a series of 20 quinoxaline-derived chalcones, based on an initial screening using human and rat squamous cell carcinoma lineages, representing compounds with at least one methoxy radical at the A-ring. The selected chalcones, mainly N9 and N17, displayed marked antiproliferative effects, via apoptosis and autophagy induction, with an increase of sub-G1 population and Akt inhibition. The three chalcones displayed marked in vitro antitumor effects in different protocols with standard chemotherapy drugs, with acceptable toxicity on normal cells. There was no growth retrieval, after exposure to chalcone N9 alone, in a long-term assay to determine the cumulative population doubling (CPD) of human oral cancer cells. A PCR array evaluating 168 genes related to cancer and inflammation, demonstrated striking actions for N9, which altered the expression of 74 genes. Altogether, our results point out quinoxalinic chalcones, mainly N9, as potential strategies for oral cancer treatment.application/pdfengScientific reports. London. Vol. 7 (2017), article 15850, [16] f.QuinoxalinasNeoplasias bucaisChalconasOral cancerMechanisms underlying the antiproliferative effects of a series of quinoxaline-derived chalconesEstrangeiroinfo:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFRGSinstname:Universidade Federal do Rio Grande do Sul (UFRGS)instacron:UFRGSTEXT001087295.pdf.txt001087295.pdf.txtExtracted Texttext/plain74178http://www.lume.ufrgs.br/bitstream/10183/188813/2/001087295.pdf.txtcd39b022ab46f76996b07f6705c471b5MD52ORIGINAL001087295.pdfTexto completo (inglês)application/pdf6692805http://www.lume.ufrgs.br/bitstream/10183/188813/1/001087295.pdfe6c65862102485b0766cabca12b75b2cMD5110183/1888132024-05-01 06:51:13.258374oai:www.lume.ufrgs.br:10183/188813Repositório de PublicaçõesPUBhttps://lume.ufrgs.br/oai/requestopendoar:2024-05-01T09:51:13Repositório Institucional da UFRGS - Universidade Federal do Rio Grande do Sul (UFRGS)false |
dc.title.pt_BR.fl_str_mv |
Mechanisms underlying the antiproliferative effects of a series of quinoxaline-derived chalcones |
title |
Mechanisms underlying the antiproliferative effects of a series of quinoxaline-derived chalcones |
spellingShingle |
Mechanisms underlying the antiproliferative effects of a series of quinoxaline-derived chalcones Mielcke, Tânia Regina Quinoxalinas Neoplasias bucais Chalconas Oral cancer |
title_short |
Mechanisms underlying the antiproliferative effects of a series of quinoxaline-derived chalcones |
title_full |
Mechanisms underlying the antiproliferative effects of a series of quinoxaline-derived chalcones |
title_fullStr |
Mechanisms underlying the antiproliferative effects of a series of quinoxaline-derived chalcones |
title_full_unstemmed |
Mechanisms underlying the antiproliferative effects of a series of quinoxaline-derived chalcones |
title_sort |
Mechanisms underlying the antiproliferative effects of a series of quinoxaline-derived chalcones |
author |
Mielcke, Tânia Regina |
author_facet |
Mielcke, Tânia Regina Muradás, Thaís Cristina Chiela, Eduardo Cremonese Filippi Amaral, Maria Eduarda Azambuja Kist, Luiza Wilges Bogo, Mauricio Reis Mascarello, Alessandra Neuenfeldt, Patrícia Devantier Nunes, Ricardo José Campos, Maria Martha |
author_role |
author |
author2 |
Muradás, Thaís Cristina Chiela, Eduardo Cremonese Filippi Amaral, Maria Eduarda Azambuja Kist, Luiza Wilges Bogo, Mauricio Reis Mascarello, Alessandra Neuenfeldt, Patrícia Devantier Nunes, Ricardo José Campos, Maria Martha |
author2_role |
author author author author author author author author author |
dc.contributor.author.fl_str_mv |
Mielcke, Tânia Regina Muradás, Thaís Cristina Chiela, Eduardo Cremonese Filippi Amaral, Maria Eduarda Azambuja Kist, Luiza Wilges Bogo, Mauricio Reis Mascarello, Alessandra Neuenfeldt, Patrícia Devantier Nunes, Ricardo José Campos, Maria Martha |
dc.subject.por.fl_str_mv |
Quinoxalinas Neoplasias bucais Chalconas |
topic |
Quinoxalinas Neoplasias bucais Chalconas Oral cancer |
dc.subject.eng.fl_str_mv |
Oral cancer |
description |
The present study aimed to characterize the effects of quinoxaline-derived chalcones, designed on the basis of the selective PI3Kγ inhibitor AS605240, in oral cancer cells. Three lead compounds, namely N9, N17 and N23, were selected from a series of 20 quinoxaline-derived chalcones, based on an initial screening using human and rat squamous cell carcinoma lineages, representing compounds with at least one methoxy radical at the A-ring. The selected chalcones, mainly N9 and N17, displayed marked antiproliferative effects, via apoptosis and autophagy induction, with an increase of sub-G1 population and Akt inhibition. The three chalcones displayed marked in vitro antitumor effects in different protocols with standard chemotherapy drugs, with acceptable toxicity on normal cells. There was no growth retrieval, after exposure to chalcone N9 alone, in a long-term assay to determine the cumulative population doubling (CPD) of human oral cancer cells. A PCR array evaluating 168 genes related to cancer and inflammation, demonstrated striking actions for N9, which altered the expression of 74 genes. Altogether, our results point out quinoxalinic chalcones, mainly N9, as potential strategies for oral cancer treatment. |
publishDate |
2017 |
dc.date.issued.fl_str_mv |
2017 |
dc.date.accessioned.fl_str_mv |
2019-02-15T02:33:45Z |
dc.type.driver.fl_str_mv |
Estrangeiro info:eu-repo/semantics/article |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
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article |
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publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10183/188813 |
dc.identifier.issn.pt_BR.fl_str_mv |
2045-2322 |
dc.identifier.nrb.pt_BR.fl_str_mv |
001087295 |
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2045-2322 001087295 |
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http://hdl.handle.net/10183/188813 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.ispartof.pt_BR.fl_str_mv |
Scientific reports. London. Vol. 7 (2017), article 15850, [16] f. |
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info:eu-repo/semantics/openAccess |
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openAccess |
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application/pdf |
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