Betulinic acid-brosimine B hybrid compound has a synergistic effect with imatinib in chronic myeloid leukemia cell line, modulating apoptosis and autophagy
Autor(a) principal: | |
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Data de Publicação: | 2023 |
Outros Autores: | , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UFRGS |
Texto Completo: | http://hdl.handle.net/10183/259140 |
Resumo: | Chronic myeloid leukemia (CML) is a myeloproliferative disease characterized by the formation of the BCR-ABL (breakpoint cluster region-Abelson) oncoprotein. As many patients display therapeutic resistance, the development of new drugs based on semisynthetic products represents a new potential therapeutic approach for treating the disease. In this study, we investigated the cytotoxic activity, possible mechanism of action of a hybrid compound of betulinic acid (BA) and brosimine B in CML cell lines that are sensitive (K-562) and resistant (K-562R) to imatinib, in addition to evaluating lower doses of imatinib in combination with the hybrid compound. The effects of the compound, and its combination with imatinib, on apoptosis, cell cycle, autophagy and oxidative stress were determined. The compound was cytotoxic in K-562 (23.57 2.87 M) and K-562R (25.80 3.21 M) cells, and a synergistic effect was observed when it was associated with imatinib. Apoptosis was mediated by the caspase 3 and 9 intrinsic pathway, and cell cycle evaluation showed arrest at G0/G1. In addition, the hybrid compound increased the production of reactive oxygen species and induced autophagy by increasing LC3II and Beclin-1 mRNA levels. Results suggest that this hybrid compound causes the death of both imatinib-sensitive and -resistant cell lines and may hold potential as a new anticancer treatment against CML. |
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Willig, Julia BizCouto, Nádia Miléo Garcês deVianna, Débora Renz BarretoMariot, Camila da SilveiraGnoatto, Simone Cristina BaggioBuffon, AndreiaPilger, Diogo Andre2023-06-17T03:38:05Z20231424-8247http://hdl.handle.net/10183/259140001166955Chronic myeloid leukemia (CML) is a myeloproliferative disease characterized by the formation of the BCR-ABL (breakpoint cluster region-Abelson) oncoprotein. As many patients display therapeutic resistance, the development of new drugs based on semisynthetic products represents a new potential therapeutic approach for treating the disease. In this study, we investigated the cytotoxic activity, possible mechanism of action of a hybrid compound of betulinic acid (BA) and brosimine B in CML cell lines that are sensitive (K-562) and resistant (K-562R) to imatinib, in addition to evaluating lower doses of imatinib in combination with the hybrid compound. The effects of the compound, and its combination with imatinib, on apoptosis, cell cycle, autophagy and oxidative stress were determined. The compound was cytotoxic in K-562 (23.57 2.87 M) and K-562R (25.80 3.21 M) cells, and a synergistic effect was observed when it was associated with imatinib. Apoptosis was mediated by the caspase 3 and 9 intrinsic pathway, and cell cycle evaluation showed arrest at G0/G1. In addition, the hybrid compound increased the production of reactive oxygen species and induced autophagy by increasing LC3II and Beclin-1 mRNA levels. Results suggest that this hybrid compound causes the death of both imatinib-sensitive and -resistant cell lines and may hold potential as a new anticancer treatment against CML.application/pdfengPharmaceuticals. Basel. Vol. 16, n. 4 (2023), 586, 17 p.Ácido betulínicoMesilato de imatinibSinergismo farmacológicoLeucemia mielogênica crônica BCR-ABL positivaBetulinic acidBrosimine BImatinibSynergismK-562Chronic myeloid leukemiaBetulinic acid-brosimine B hybrid compound has a synergistic effect with imatinib in chronic myeloid leukemia cell line, modulating apoptosis and autophagyEstrangeiroinfo: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:UFRGSTEXT001166955.pdf.txt001166955.pdf.txtExtracted Texttext/plain58666http://www.lume.ufrgs.br/bitstream/10183/259140/2/001166955.pdf.txt53c5d51ff0092e90afc930b891a94db3MD52ORIGINAL001166955.pdfTexto completo (inglês)application/pdf3368901http://www.lume.ufrgs.br/bitstream/10183/259140/1/001166955.pdff375e72ada5710f1f32009c3c3f6b994MD5110183/2591402023-06-18 03:52:38.836013oai:www.lume.ufrgs.br:10183/259140Repositório de PublicaçõesPUBhttps://lume.ufrgs.br/oai/requestopendoar:2023-06-18T06:52:38Repositório Institucional da UFRGS - Universidade Federal do Rio Grande do Sul (UFRGS)false |
dc.title.pt_BR.fl_str_mv |
Betulinic acid-brosimine B hybrid compound has a synergistic effect with imatinib in chronic myeloid leukemia cell line, modulating apoptosis and autophagy |
title |
Betulinic acid-brosimine B hybrid compound has a synergistic effect with imatinib in chronic myeloid leukemia cell line, modulating apoptosis and autophagy |
spellingShingle |
Betulinic acid-brosimine B hybrid compound has a synergistic effect with imatinib in chronic myeloid leukemia cell line, modulating apoptosis and autophagy Willig, Julia Biz Ácido betulínico Mesilato de imatinib Sinergismo farmacológico Leucemia mielogênica crônica BCR-ABL positiva Betulinic acid Brosimine B Imatinib Synergism K-562 Chronic myeloid leukemia |
title_short |
Betulinic acid-brosimine B hybrid compound has a synergistic effect with imatinib in chronic myeloid leukemia cell line, modulating apoptosis and autophagy |
title_full |
Betulinic acid-brosimine B hybrid compound has a synergistic effect with imatinib in chronic myeloid leukemia cell line, modulating apoptosis and autophagy |
title_fullStr |
Betulinic acid-brosimine B hybrid compound has a synergistic effect with imatinib in chronic myeloid leukemia cell line, modulating apoptosis and autophagy |
title_full_unstemmed |
Betulinic acid-brosimine B hybrid compound has a synergistic effect with imatinib in chronic myeloid leukemia cell line, modulating apoptosis and autophagy |
title_sort |
Betulinic acid-brosimine B hybrid compound has a synergistic effect with imatinib in chronic myeloid leukemia cell line, modulating apoptosis and autophagy |
author |
Willig, Julia Biz |
author_facet |
Willig, Julia Biz Couto, Nádia Miléo Garcês de Vianna, Débora Renz Barreto Mariot, Camila da Silveira Gnoatto, Simone Cristina Baggio Buffon, Andreia Pilger, Diogo Andre |
author_role |
author |
author2 |
Couto, Nádia Miléo Garcês de Vianna, Débora Renz Barreto Mariot, Camila da Silveira Gnoatto, Simone Cristina Baggio Buffon, Andreia Pilger, Diogo Andre |
author2_role |
author author author author author author |
dc.contributor.author.fl_str_mv |
Willig, Julia Biz Couto, Nádia Miléo Garcês de Vianna, Débora Renz Barreto Mariot, Camila da Silveira Gnoatto, Simone Cristina Baggio Buffon, Andreia Pilger, Diogo Andre |
dc.subject.por.fl_str_mv |
Ácido betulínico Mesilato de imatinib Sinergismo farmacológico Leucemia mielogênica crônica BCR-ABL positiva |
topic |
Ácido betulínico Mesilato de imatinib Sinergismo farmacológico Leucemia mielogênica crônica BCR-ABL positiva Betulinic acid Brosimine B Imatinib Synergism K-562 Chronic myeloid leukemia |
dc.subject.eng.fl_str_mv |
Betulinic acid Brosimine B Imatinib Synergism K-562 Chronic myeloid leukemia |
description |
Chronic myeloid leukemia (CML) is a myeloproliferative disease characterized by the formation of the BCR-ABL (breakpoint cluster region-Abelson) oncoprotein. As many patients display therapeutic resistance, the development of new drugs based on semisynthetic products represents a new potential therapeutic approach for treating the disease. In this study, we investigated the cytotoxic activity, possible mechanism of action of a hybrid compound of betulinic acid (BA) and brosimine B in CML cell lines that are sensitive (K-562) and resistant (K-562R) to imatinib, in addition to evaluating lower doses of imatinib in combination with the hybrid compound. The effects of the compound, and its combination with imatinib, on apoptosis, cell cycle, autophagy and oxidative stress were determined. The compound was cytotoxic in K-562 (23.57 2.87 M) and K-562R (25.80 3.21 M) cells, and a synergistic effect was observed when it was associated with imatinib. Apoptosis was mediated by the caspase 3 and 9 intrinsic pathway, and cell cycle evaluation showed arrest at G0/G1. In addition, the hybrid compound increased the production of reactive oxygen species and induced autophagy by increasing LC3II and Beclin-1 mRNA levels. Results suggest that this hybrid compound causes the death of both imatinib-sensitive and -resistant cell lines and may hold potential as a new anticancer treatment against CML. |
publishDate |
2023 |
dc.date.accessioned.fl_str_mv |
2023-06-17T03:38:05Z |
dc.date.issued.fl_str_mv |
2023 |
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/10183/259140 |
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1424-8247 |
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001166955 |
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http://hdl.handle.net/10183/259140 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.ispartof.pt_BR.fl_str_mv |
Pharmaceuticals. Basel. Vol. 16, n. 4 (2023), 586, 17 p. |
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openAccess |
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