Epigenetic targeting drugs potentiate chemotherapeutic effects in solid tumor therapy

Abstract Epigenetic therapy is a novel tumor therapeutic method and refers to the targeting of the aberrant epigenetic modifications presumably at cancer-related genes by chemicals which are epigenetic targeting drugs (ETDs). Not like in treating hematopoietic cancer, the clinical trials investigati...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Jingjing Li, Dapeng Hao, Li Wang, Haitao Wang, Yuan Wang, Zhiqiang Zhao, Peipei Li, Chuxia Deng, Li-jun Di
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/4bf5605205bc40e6b54e133cb3db3020
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:4bf5605205bc40e6b54e133cb3db3020
record_format	dspace
spelling	oai:doaj.org-article:4bf5605205bc40e6b54e133cb3db30202021-12-02T11:53:04ZEpigenetic targeting drugs potentiate chemotherapeutic effects in solid tumor therapy10.1038/s41598-017-04406-02045-2322https://doaj.org/article/4bf5605205bc40e6b54e133cb3db30202017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-04406-0https://doaj.org/toc/2045-2322Abstract Epigenetic therapy is a novel tumor therapeutic method and refers to the targeting of the aberrant epigenetic modifications presumably at cancer-related genes by chemicals which are epigenetic targeting drugs (ETDs). Not like in treating hematopoietic cancer, the clinical trials investigating the potential use of ETDs in the solid tumor is not encouraging. Instead, the curative effects of ETD delivered together with DNA targeting chemo drugs (DTDs) are quite promising according to our meta-analysis. To investigate the synergistic mechanism of ETD and DTD drug combination, the therapeutic effect was studied using both cell lines and mouse engrafted tumors. Mechanically we show that HDAC inhibitors and DNMT inhibitors are capable of increasing the chromatin accessibility to cisplatin (CP) and doxorubicin (Dox) through chromatin decompaction globally. Consequently, the combination of ETD and DTD enhances the DTD induced DNA damage and cell death. Engrafted tumors in SCID mice also show increased sensitivity to irradiation (IR) or CP when the tumors were pretreated by ETDs. Given the limited therapeutic effect of ETD alone, these results strongly suggest that the combination of DTD, including irradiation, and ETD treatment is a very promising choice in clinical solid tumor therapy.Jingjing LiDapeng HaoLi WangHaitao WangYuan WangZhiqiang ZhaoPeipei LiChuxia DengLi-jun DiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-13 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jingjing Li Dapeng Hao Li Wang Haitao Wang Yuan Wang Zhiqiang Zhao Peipei Li Chuxia Deng Li-jun Di Epigenetic targeting drugs potentiate chemotherapeutic effects in solid tumor therapy
description	Abstract Epigenetic therapy is a novel tumor therapeutic method and refers to the targeting of the aberrant epigenetic modifications presumably at cancer-related genes by chemicals which are epigenetic targeting drugs (ETDs). Not like in treating hematopoietic cancer, the clinical trials investigating the potential use of ETDs in the solid tumor is not encouraging. Instead, the curative effects of ETD delivered together with DNA targeting chemo drugs (DTDs) are quite promising according to our meta-analysis. To investigate the synergistic mechanism of ETD and DTD drug combination, the therapeutic effect was studied using both cell lines and mouse engrafted tumors. Mechanically we show that HDAC inhibitors and DNMT inhibitors are capable of increasing the chromatin accessibility to cisplatin (CP) and doxorubicin (Dox) through chromatin decompaction globally. Consequently, the combination of ETD and DTD enhances the DTD induced DNA damage and cell death. Engrafted tumors in SCID mice also show increased sensitivity to irradiation (IR) or CP when the tumors were pretreated by ETDs. Given the limited therapeutic effect of ETD alone, these results strongly suggest that the combination of DTD, including irradiation, and ETD treatment is a very promising choice in clinical solid tumor therapy.
format	article
author	Jingjing Li Dapeng Hao Li Wang Haitao Wang Yuan Wang Zhiqiang Zhao Peipei Li Chuxia Deng Li-jun Di
author_facet	Jingjing Li Dapeng Hao Li Wang Haitao Wang Yuan Wang Zhiqiang Zhao Peipei Li Chuxia Deng Li-jun Di
author_sort	Jingjing Li
title	Epigenetic targeting drugs potentiate chemotherapeutic effects in solid tumor therapy
title_short	Epigenetic targeting drugs potentiate chemotherapeutic effects in solid tumor therapy
title_full	Epigenetic targeting drugs potentiate chemotherapeutic effects in solid tumor therapy
title_fullStr	Epigenetic targeting drugs potentiate chemotherapeutic effects in solid tumor therapy
title_full_unstemmed	Epigenetic targeting drugs potentiate chemotherapeutic effects in solid tumor therapy
title_sort	epigenetic targeting drugs potentiate chemotherapeutic effects in solid tumor therapy
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/4bf5605205bc40e6b54e133cb3db3020
work_keys_str_mv	AT jingjingli epigenetictargetingdrugspotentiatechemotherapeuticeffectsinsolidtumortherapy AT dapenghao epigenetictargetingdrugspotentiatechemotherapeuticeffectsinsolidtumortherapy AT liwang epigenetictargetingdrugspotentiatechemotherapeuticeffectsinsolidtumortherapy AT haitaowang epigenetictargetingdrugspotentiatechemotherapeuticeffectsinsolidtumortherapy AT yuanwang epigenetictargetingdrugspotentiatechemotherapeuticeffectsinsolidtumortherapy AT zhiqiangzhao epigenetictargetingdrugspotentiatechemotherapeuticeffectsinsolidtumortherapy AT peipeili epigenetictargetingdrugspotentiatechemotherapeuticeffectsinsolidtumortherapy AT chuxiadeng epigenetictargetingdrugspotentiatechemotherapeuticeffectsinsolidtumortherapy AT lijundi epigenetictargetingdrugspotentiatechemotherapeuticeffectsinsolidtumortherapy
_version_	1718394864553426944

Epigenetic targeting drugs potentiate chemotherapeutic effects in solid tumor therapy

Ejemplares similares