Unlocking the chromatin of adenoid cystic carcinomas using HDAC inhibitors sensitize cancer stem cells to cisplatin and induces tumor senescence
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/10183/184001 |
Resumo: | Adenoid cystic carcinoma (ACC) is an uncommonmalignancy of the salivary glands that is characterized by local recurrence and distant metastasis due to its resistance to conventional therapy. Platinum-based therapies have been extensively explored as a treatment for ACC, but they show little effectiveness. Studies have shown that a specific group of tumor cells, harboring characteristics of cancer stem cells (CSCs), are involved in chemoresistance of myeloid leukemias, breast, colorectal and pancreatic carcinomas. Therapeutic strategies that target CSCs improve the survival of patients by decreasing the rates of tumor relapse, and epigenetic drugs, such as histone deacetylase inhibitors (HDACi), have shown promising results in targeting CSCs. In this study, we investigated the effect of the HDACi Suberoylanilide hydroxamic acid (Vorinostat), and cisplatin, alone or in combination, on CSCs and non-CSCs from ACC.We used CSCs as a biological marker for tumor resistance to therapy in patient-derived xenograft (PDX) samples and ACC primary cells.We found that cisplatin reduced tumor viability, but enriched the population of CSCs. Systemic administration of Vorinostat reduced the number of detectable CSCs in vivo and in vitro, and a low dose of Vorinostat decreased tumor cell viability. However, the combination of Vorinostat and cisplatin was extremely effective in depleting CSCs and reducing tumor viability in all ACC primary cells by activating cellular senescence. These observations suggest that HDACi and intercalating agents act more efficiently in combination to destroy tumor cells and their stem cells. |
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Almeida, Luciana OliveiraGuimarães, Douglas M.Martins, Manoela DominguesMartins, Marco Antonio TrevizaniWarner, KristyNor, Jacques EduardoCastilho, Rogerio MoraesSquarize, Cristiane Helena2018-10-26T02:43:33Z20171876-7753http://hdl.handle.net/10183/184001001058897Adenoid cystic carcinoma (ACC) is an uncommonmalignancy of the salivary glands that is characterized by local recurrence and distant metastasis due to its resistance to conventional therapy. Platinum-based therapies have been extensively explored as a treatment for ACC, but they show little effectiveness. Studies have shown that a specific group of tumor cells, harboring characteristics of cancer stem cells (CSCs), are involved in chemoresistance of myeloid leukemias, breast, colorectal and pancreatic carcinomas. Therapeutic strategies that target CSCs improve the survival of patients by decreasing the rates of tumor relapse, and epigenetic drugs, such as histone deacetylase inhibitors (HDACi), have shown promising results in targeting CSCs. In this study, we investigated the effect of the HDACi Suberoylanilide hydroxamic acid (Vorinostat), and cisplatin, alone or in combination, on CSCs and non-CSCs from ACC.We used CSCs as a biological marker for tumor resistance to therapy in patient-derived xenograft (PDX) samples and ACC primary cells.We found that cisplatin reduced tumor viability, but enriched the population of CSCs. Systemic administration of Vorinostat reduced the number of detectable CSCs in vivo and in vitro, and a low dose of Vorinostat decreased tumor cell viability. However, the combination of Vorinostat and cisplatin was extremely effective in depleting CSCs and reducing tumor viability in all ACC primary cells by activating cellular senescence. These observations suggest that HDACi and intercalating agents act more efficiently in combination to destroy tumor cells and their stem cells.application/pdfengStem cell research. Kidlington. Vol. 21 (May 2017), p. 91-105Carcinoma adenoide císticoCélulas-tronco neoplásicasPatologia bucalAdenoid cystic carcinomaCancer stem cellsChemoresistanceVorinostatCisplatinUnlocking the chromatin of adenoid cystic carcinomas using HDAC inhibitors sensitize cancer stem cells to cisplatin and induces tumor senescenceEstrangeiroinfo: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:UFRGSORIGINAL001058897.pdfTexto completo (inglês)application/pdf2269430http://www.lume.ufrgs.br/bitstream/10183/184001/1/001058897.pdfaeac1c9a7497691b467566d08efaad66MD51TEXT001058897.pdf.txt001058897.pdf.txtExtracted Texttext/plain61179http://www.lume.ufrgs.br/bitstream/10183/184001/2/001058897.pdf.txte5df3aea62f2a710ce2bdec6f80fce24MD52THUMBNAIL001058897.pdf.jpg001058897.pdf.jpgGenerated Thumbnailimage/jpeg1943http://www.lume.ufrgs.br/bitstream/10183/184001/3/001058897.pdf.jpgdecd7a792f6ca26190aead439a7430efMD5310183/1840012018-10-27 03:12:46.958024oai:www.lume.ufrgs.br:10183/184001Repositório de PublicaçõesPUBhttps://lume.ufrgs.br/oai/requestopendoar:2018-10-27T06:12:46Repositório Institucional da UFRGS - Universidade Federal do Rio Grande do Sul (UFRGS)false |
dc.title.pt_BR.fl_str_mv |
Unlocking the chromatin of adenoid cystic carcinomas using HDAC inhibitors sensitize cancer stem cells to cisplatin and induces tumor senescence |
title |
Unlocking the chromatin of adenoid cystic carcinomas using HDAC inhibitors sensitize cancer stem cells to cisplatin and induces tumor senescence |
spellingShingle |
Unlocking the chromatin of adenoid cystic carcinomas using HDAC inhibitors sensitize cancer stem cells to cisplatin and induces tumor senescence Almeida, Luciana Oliveira Carcinoma adenoide cístico Células-tronco neoplásicas Patologia bucal Adenoid cystic carcinoma Cancer stem cells Chemoresistance Vorinostat Cisplatin |
title_short |
Unlocking the chromatin of adenoid cystic carcinomas using HDAC inhibitors sensitize cancer stem cells to cisplatin and induces tumor senescence |
title_full |
Unlocking the chromatin of adenoid cystic carcinomas using HDAC inhibitors sensitize cancer stem cells to cisplatin and induces tumor senescence |
title_fullStr |
Unlocking the chromatin of adenoid cystic carcinomas using HDAC inhibitors sensitize cancer stem cells to cisplatin and induces tumor senescence |
title_full_unstemmed |
Unlocking the chromatin of adenoid cystic carcinomas using HDAC inhibitors sensitize cancer stem cells to cisplatin and induces tumor senescence |
title_sort |
Unlocking the chromatin of adenoid cystic carcinomas using HDAC inhibitors sensitize cancer stem cells to cisplatin and induces tumor senescence |
author |
Almeida, Luciana Oliveira |
author_facet |
Almeida, Luciana Oliveira Guimarães, Douglas M. Martins, Manoela Domingues Martins, Marco Antonio Trevizani Warner, Kristy Nor, Jacques Eduardo Castilho, Rogerio Moraes Squarize, Cristiane Helena |
author_role |
author |
author2 |
Guimarães, Douglas M. Martins, Manoela Domingues Martins, Marco Antonio Trevizani Warner, Kristy Nor, Jacques Eduardo Castilho, Rogerio Moraes Squarize, Cristiane Helena |
author2_role |
author author author author author author author |
dc.contributor.author.fl_str_mv |
Almeida, Luciana Oliveira Guimarães, Douglas M. Martins, Manoela Domingues Martins, Marco Antonio Trevizani Warner, Kristy Nor, Jacques Eduardo Castilho, Rogerio Moraes Squarize, Cristiane Helena |
dc.subject.por.fl_str_mv |
Carcinoma adenoide cístico Células-tronco neoplásicas Patologia bucal |
topic |
Carcinoma adenoide cístico Células-tronco neoplásicas Patologia bucal Adenoid cystic carcinoma Cancer stem cells Chemoresistance Vorinostat Cisplatin |
dc.subject.eng.fl_str_mv |
Adenoid cystic carcinoma Cancer stem cells Chemoresistance Vorinostat Cisplatin |
description |
Adenoid cystic carcinoma (ACC) is an uncommonmalignancy of the salivary glands that is characterized by local recurrence and distant metastasis due to its resistance to conventional therapy. Platinum-based therapies have been extensively explored as a treatment for ACC, but they show little effectiveness. Studies have shown that a specific group of tumor cells, harboring characteristics of cancer stem cells (CSCs), are involved in chemoresistance of myeloid leukemias, breast, colorectal and pancreatic carcinomas. Therapeutic strategies that target CSCs improve the survival of patients by decreasing the rates of tumor relapse, and epigenetic drugs, such as histone deacetylase inhibitors (HDACi), have shown promising results in targeting CSCs. In this study, we investigated the effect of the HDACi Suberoylanilide hydroxamic acid (Vorinostat), and cisplatin, alone or in combination, on CSCs and non-CSCs from ACC.We used CSCs as a biological marker for tumor resistance to therapy in patient-derived xenograft (PDX) samples and ACC primary cells.We found that cisplatin reduced tumor viability, but enriched the population of CSCs. Systemic administration of Vorinostat reduced the number of detectable CSCs in vivo and in vitro, and a low dose of Vorinostat decreased tumor cell viability. However, the combination of Vorinostat and cisplatin was extremely effective in depleting CSCs and reducing tumor viability in all ACC primary cells by activating cellular senescence. These observations suggest that HDACi and intercalating agents act more efficiently in combination to destroy tumor cells and their stem cells. |
publishDate |
2017 |
dc.date.issued.fl_str_mv |
2017 |
dc.date.accessioned.fl_str_mv |
2018-10-26T02:43:33Z |
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publishedVersion |
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http://hdl.handle.net/10183/184001 |
dc.identifier.issn.pt_BR.fl_str_mv |
1876-7753 |
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001058897 |
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http://hdl.handle.net/10183/184001 |
dc.language.iso.fl_str_mv |
eng |
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dc.relation.ispartof.pt_BR.fl_str_mv |
Stem cell research. Kidlington. Vol. 21 (May 2017), p. 91-105 |
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openAccess |
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