Unusual dimeric flavonoids (brachydins) induce ultrastructural membrane alterations associated with antitumor activity in cancer cell lines
Autor(a) principal: | |
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Data de Publicação: | 2022 |
Outros Autores: | , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.1080/01480545.2022.2080217 http://hdl.handle.net/11449/240214 |
Resumo: | Notwithstanding the advances in molecular target-based drugs, chemotherapy remains the most common cancer treatment, despite its high toxicity. Consequently, effective anticancer therapies with fewer adverse effects are needed. Therefore, this study aimed to determine the anticancer activity of the dichloromethane fraction (DCMF) isolated from Arrabidae brachypoda roots, whose components are three unusual dimeric flavonoids. The toxicity of DCMF was investigated in breast (MCF-7), prostate (DU145), and cervical (HeLa) tumor cells, as well as non-tumor cells (PNT2), using sulforhodamine B (cell viability), Comet (genotoxicity), clonogenicity (reproductive capacity) and wound healing (cell migration) assays, and atomic force microscopy (AFM) for ultrastructural cell membrane alterations. Molecular docking revealed affinity between albumin and each rare flavonoid, supporting the impact of fetal bovine serum in DCMF antitumor activity. The IC50 values for MCF7, HeLa, and DU145 were 2.77, 2.46, and 2.51 µg/mL, respectively, and 4.08 µg/mL for PNT2. DCFM was not genotoxic to tumor or normal cells when exposed to twice the IC50 for up to 24 h, but it inhibited tumor cell migration and reproduction compared to normal cells. Additionally, AFM revealed alterations in the ultrastructure of tumor nuclear membrane surfaces, with a positive correlation between DCMF concentration and tumor cell roughness. Finally, we found a negative correlation between roughness and the ability of DCMF-treated tumor cells to migrate and form colonies with more than 50 cells. These findings suggest that DCFM acts by causing ultrastructural changes in tumor cell membranes while having fewer toxicological effects on normal cells. |
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Unusual dimeric flavonoids (brachydins) induce ultrastructural membrane alterations associated with antitumor activity in cancer cell linesArrabidaea brachypodaatomic force microscopecell membranechemotherapynatural productsNotwithstanding the advances in molecular target-based drugs, chemotherapy remains the most common cancer treatment, despite its high toxicity. Consequently, effective anticancer therapies with fewer adverse effects are needed. Therefore, this study aimed to determine the anticancer activity of the dichloromethane fraction (DCMF) isolated from Arrabidae brachypoda roots, whose components are three unusual dimeric flavonoids. The toxicity of DCMF was investigated in breast (MCF-7), prostate (DU145), and cervical (HeLa) tumor cells, as well as non-tumor cells (PNT2), using sulforhodamine B (cell viability), Comet (genotoxicity), clonogenicity (reproductive capacity) and wound healing (cell migration) assays, and atomic force microscopy (AFM) for ultrastructural cell membrane alterations. Molecular docking revealed affinity between albumin and each rare flavonoid, supporting the impact of fetal bovine serum in DCMF antitumor activity. The IC50 values for MCF7, HeLa, and DU145 were 2.77, 2.46, and 2.51 µg/mL, respectively, and 4.08 µg/mL for PNT2. DCFM was not genotoxic to tumor or normal cells when exposed to twice the IC50 for up to 24 h, but it inhibited tumor cell migration and reproduction compared to normal cells. Additionally, AFM revealed alterations in the ultrastructure of tumor nuclear membrane surfaces, with a positive correlation between DCMF concentration and tumor cell roughness. Finally, we found a negative correlation between roughness and the ability of DCMF-treated tumor cells to migrate and form colonies with more than 50 cells. These findings suggest that DCFM acts by causing ultrastructural changes in tumor cell membranes while having fewer toxicological effects on normal cells.Postgraduate Program in Biodiversity and Biotechnology-Bionorte Federal University of MaranhãoLaboratory of Genetics and Molecular Biology Department of Biology Federal University of MaranhãoDepartment of Biology State University of MaranhãoLaboratory of Natural Products Department of Chemistry Federal University of MaranhãoLaboratory of Biophysics and Nanosystems Department of Physics Federal University of MaranhãoLaboratory of Immunology Applied to Cancer Department of Physiological Sciences Federal University of MaranhãoPostgraduate Program in Health Sciences Federal University of MaranhãoPostgraduate Program in Chemistry São Paulo State University (Unesp) Institute of ChemistryPostgraduate Program in Chemistry São Paulo State University (Unesp) Institute of ChemistryFederal University of MaranhãoState University of MaranhãoUniversidade Estadual Paulista (UNESP)Maciel-Silva, Vera LuciaRocha, Claudia Quintino daAlencar, Luciana Magalhães RebeloCastelo-Branco, Patrícia ValériaSousa, Israel Higino deAzevedo-Santos, Ana PaulaVale, André Alvares MarquesMonteiro, Silvio GomesSoares, Rossy-Eric PereiraGuimarães, Sulayne Janayna AraujoNascimento, Jessyane Rodrigues do [UNESP]Pereira, Silma Regina Ferreira2023-03-01T20:06:49Z2023-03-01T20:06:49Z2022-01-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://dx.doi.org/10.1080/01480545.2022.2080217Drug and Chemical Toxicology.1525-60140148-0545http://hdl.handle.net/11449/24021410.1080/01480545.2022.20802172-s2.0-85131639405Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengDrug and Chemical Toxicologyinfo:eu-repo/semantics/openAccess2023-03-01T20:06:49Zoai:repositorio.unesp.br:11449/240214Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462023-03-01T20:06:49Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
Unusual dimeric flavonoids (brachydins) induce ultrastructural membrane alterations associated with antitumor activity in cancer cell lines |
title |
Unusual dimeric flavonoids (brachydins) induce ultrastructural membrane alterations associated with antitumor activity in cancer cell lines |
spellingShingle |
Unusual dimeric flavonoids (brachydins) induce ultrastructural membrane alterations associated with antitumor activity in cancer cell lines Maciel-Silva, Vera Lucia Arrabidaea brachypoda atomic force microscope cell membrane chemotherapy natural products |
title_short |
Unusual dimeric flavonoids (brachydins) induce ultrastructural membrane alterations associated with antitumor activity in cancer cell lines |
title_full |
Unusual dimeric flavonoids (brachydins) induce ultrastructural membrane alterations associated with antitumor activity in cancer cell lines |
title_fullStr |
Unusual dimeric flavonoids (brachydins) induce ultrastructural membrane alterations associated with antitumor activity in cancer cell lines |
title_full_unstemmed |
Unusual dimeric flavonoids (brachydins) induce ultrastructural membrane alterations associated with antitumor activity in cancer cell lines |
title_sort |
Unusual dimeric flavonoids (brachydins) induce ultrastructural membrane alterations associated with antitumor activity in cancer cell lines |
author |
Maciel-Silva, Vera Lucia |
author_facet |
Maciel-Silva, Vera Lucia Rocha, Claudia Quintino da Alencar, Luciana Magalhães Rebelo Castelo-Branco, Patrícia Valéria Sousa, Israel Higino de Azevedo-Santos, Ana Paula Vale, André Alvares Marques Monteiro, Silvio Gomes Soares, Rossy-Eric Pereira Guimarães, Sulayne Janayna Araujo Nascimento, Jessyane Rodrigues do [UNESP] Pereira, Silma Regina Ferreira |
author_role |
author |
author2 |
Rocha, Claudia Quintino da Alencar, Luciana Magalhães Rebelo Castelo-Branco, Patrícia Valéria Sousa, Israel Higino de Azevedo-Santos, Ana Paula Vale, André Alvares Marques Monteiro, Silvio Gomes Soares, Rossy-Eric Pereira Guimarães, Sulayne Janayna Araujo Nascimento, Jessyane Rodrigues do [UNESP] Pereira, Silma Regina Ferreira |
author2_role |
author author author author author author author author author author author |
dc.contributor.none.fl_str_mv |
Federal University of Maranhão State University of Maranhão Universidade Estadual Paulista (UNESP) |
dc.contributor.author.fl_str_mv |
Maciel-Silva, Vera Lucia Rocha, Claudia Quintino da Alencar, Luciana Magalhães Rebelo Castelo-Branco, Patrícia Valéria Sousa, Israel Higino de Azevedo-Santos, Ana Paula Vale, André Alvares Marques Monteiro, Silvio Gomes Soares, Rossy-Eric Pereira Guimarães, Sulayne Janayna Araujo Nascimento, Jessyane Rodrigues do [UNESP] Pereira, Silma Regina Ferreira |
dc.subject.por.fl_str_mv |
Arrabidaea brachypoda atomic force microscope cell membrane chemotherapy natural products |
topic |
Arrabidaea brachypoda atomic force microscope cell membrane chemotherapy natural products |
description |
Notwithstanding the advances in molecular target-based drugs, chemotherapy remains the most common cancer treatment, despite its high toxicity. Consequently, effective anticancer therapies with fewer adverse effects are needed. Therefore, this study aimed to determine the anticancer activity of the dichloromethane fraction (DCMF) isolated from Arrabidae brachypoda roots, whose components are three unusual dimeric flavonoids. The toxicity of DCMF was investigated in breast (MCF-7), prostate (DU145), and cervical (HeLa) tumor cells, as well as non-tumor cells (PNT2), using sulforhodamine B (cell viability), Comet (genotoxicity), clonogenicity (reproductive capacity) and wound healing (cell migration) assays, and atomic force microscopy (AFM) for ultrastructural cell membrane alterations. Molecular docking revealed affinity between albumin and each rare flavonoid, supporting the impact of fetal bovine serum in DCMF antitumor activity. The IC50 values for MCF7, HeLa, and DU145 were 2.77, 2.46, and 2.51 µg/mL, respectively, and 4.08 µg/mL for PNT2. DCFM was not genotoxic to tumor or normal cells when exposed to twice the IC50 for up to 24 h, but it inhibited tumor cell migration and reproduction compared to normal cells. Additionally, AFM revealed alterations in the ultrastructure of tumor nuclear membrane surfaces, with a positive correlation between DCMF concentration and tumor cell roughness. Finally, we found a negative correlation between roughness and the ability of DCMF-treated tumor cells to migrate and form colonies with more than 50 cells. These findings suggest that DCFM acts by causing ultrastructural changes in tumor cell membranes while having fewer toxicological effects on normal cells. |
publishDate |
2022 |
dc.date.none.fl_str_mv |
2022-01-01 2023-03-01T20:06:49Z 2023-03-01T20:06:49Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://dx.doi.org/10.1080/01480545.2022.2080217 Drug and Chemical Toxicology. 1525-6014 0148-0545 http://hdl.handle.net/11449/240214 10.1080/01480545.2022.2080217 2-s2.0-85131639405 |
url |
http://dx.doi.org/10.1080/01480545.2022.2080217 http://hdl.handle.net/11449/240214 |
identifier_str_mv |
Drug and Chemical Toxicology. 1525-6014 0148-0545 10.1080/01480545.2022.2080217 2-s2.0-85131639405 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Drug and Chemical Toxicology |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.source.none.fl_str_mv |
Scopus reponame:Repositório Institucional da UNESP instname:Universidade Estadual Paulista (UNESP) instacron:UNESP |
instname_str |
Universidade Estadual Paulista (UNESP) |
instacron_str |
UNESP |
institution |
UNESP |
reponame_str |
Repositório Institucional da UNESP |
collection |
Repositório Institucional da UNESP |
repository.name.fl_str_mv |
Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP) |
repository.mail.fl_str_mv |
|
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1797789843266207744 |