Enhancement of Tumor Cell Death by Combining gef Gene Mediated Therapy and New 1,4-Benzoxazepin-2,6-Dichloropurine Derivatives in Breast Cancer Cells
New treatment modalities are urgently needed to better manage advanced breast cancer. Combination therapies are usually more effective than monotherapy. In this context, the use of cyclic and acyclic O,N-acetals derivative compounds in combination with the suicide gef gene shown a potent anti-tumor...
Main Authors: | , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Frontiers Media S.A.
2018-07-01
|
Series: | Frontiers in Pharmacology |
Subjects: | |
Online Access: | https://www.frontiersin.org/article/10.3389/fphar.2018.00798/full |
id |
doaj-a7c46f51a3af4717b6c4c1c579b1417a |
---|---|
record_format |
Article |
spelling |
doaj-a7c46f51a3af4717b6c4c1c579b1417a2020-11-24T23:11:30ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122018-07-01910.3389/fphar.2018.00798384816Enhancement of Tumor Cell Death by Combining gef Gene Mediated Therapy and New 1,4-Benzoxazepin-2,6-Dichloropurine Derivatives in Breast Cancer CellsAlberto Ramírez0Alberto Ramírez1Ana Conejo-García2Carmen Griñán-Lisón3Carmen Griñán-Lisón4Carmen Griñán-Lisón5Luisa C. López-Cara6Gema Jiménez7Gema Jiménez8Gema Jiménez9Joaquín M. Campos10Juan A. Marchal11Juan A. Marchal12Juan A. Marchal13Houria Boulaiz14Houria Boulaiz15Houria Boulaiz16Biopathology and Medicine Regenerative Institute, University of Granada, Granada, SpainBiosanitary Institute of Granada, SAS-Universidad de Granada, Granada, SpainDepartment of Pharmaceutical and Organic Chemistry, University of Granada, Granada, SpainBiopathology and Medicine Regenerative Institute, University of Granada, Granada, SpainBiosanitary Institute of Granada, SAS-Universidad de Granada, Granada, SpainExcellence Research Unit “Modeling Nature” – Department of Human Anatomy and Embryology, University of Granada, Granada, SpainDepartment of Pharmaceutical and Organic Chemistry, University of Granada, Granada, SpainBiopathology and Medicine Regenerative Institute, University of Granada, Granada, SpainBiosanitary Institute of Granada, SAS-Universidad de Granada, Granada, SpainExcellence Research Unit “Modeling Nature” – Department of Human Anatomy and Embryology, University of Granada, Granada, SpainDepartment of Pharmaceutical and Organic Chemistry, University of Granada, Granada, SpainBiopathology and Medicine Regenerative Institute, University of Granada, Granada, SpainBiosanitary Institute of Granada, SAS-Universidad de Granada, Granada, SpainExcellence Research Unit “Modeling Nature” – Department of Human Anatomy and Embryology, University of Granada, Granada, SpainBiopathology and Medicine Regenerative Institute, University of Granada, Granada, SpainBiosanitary Institute of Granada, SAS-Universidad de Granada, Granada, SpainExcellence Research Unit “Modeling Nature” – Department of Human Anatomy and Embryology, University of Granada, Granada, SpainNew treatment modalities are urgently needed to better manage advanced breast cancer. Combination therapies are usually more effective than monotherapy. In this context, the use of cyclic and acyclic O,N-acetals derivative compounds in combination with the suicide gef gene shown a potent anti-tumor activity and represent a new generation of anticancer agents. Here, we evaluate the use of the gef gene to promote and increase the anti-tumor effect of cyclic and acyclic O,N-acetals purine derivatives and elucidate their mechanisms of action. Among all compounds tested, those with a nitro group and a cyclic pattern structures (FC-30b2, FC-29c, and bozepinib) are the most benefited from the gef gene effect. These compounds, in combination with gef gene, were able to abolish tumor cell proliferation with a minimal dose leading to more effective and less toxic chemotherapy. The effect of this combined therapy is triggered by apoptosis induction which can be found deregulated in the later stage of breast cancer. Moreover, the combined therapy leads to an increase of cell post-apoptotic secondary necrosis that is able to promote the immunogenicity of cancer cells leading to a successful treatment. This data suggests that this novel combination therapy represents a promising candidate for breast cancer treatment.https://www.frontiersin.org/article/10.3389/fphar.2018.00798/fullgef gene14-benzoxazepin-26-dichloropurinebreast cancercombined therapy |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Alberto Ramírez Alberto Ramírez Ana Conejo-García Carmen Griñán-Lisón Carmen Griñán-Lisón Carmen Griñán-Lisón Luisa C. López-Cara Gema Jiménez Gema Jiménez Gema Jiménez Joaquín M. Campos Juan A. Marchal Juan A. Marchal Juan A. Marchal Houria Boulaiz Houria Boulaiz Houria Boulaiz |
spellingShingle |
Alberto Ramírez Alberto Ramírez Ana Conejo-García Carmen Griñán-Lisón Carmen Griñán-Lisón Carmen Griñán-Lisón Luisa C. López-Cara Gema Jiménez Gema Jiménez Gema Jiménez Joaquín M. Campos Juan A. Marchal Juan A. Marchal Juan A. Marchal Houria Boulaiz Houria Boulaiz Houria Boulaiz Enhancement of Tumor Cell Death by Combining gef Gene Mediated Therapy and New 1,4-Benzoxazepin-2,6-Dichloropurine Derivatives in Breast Cancer Cells Frontiers in Pharmacology gef gene 1 4-benzoxazepin-2 6-dichloropurine breast cancer combined therapy |
author_facet |
Alberto Ramírez Alberto Ramírez Ana Conejo-García Carmen Griñán-Lisón Carmen Griñán-Lisón Carmen Griñán-Lisón Luisa C. López-Cara Gema Jiménez Gema Jiménez Gema Jiménez Joaquín M. Campos Juan A. Marchal Juan A. Marchal Juan A. Marchal Houria Boulaiz Houria Boulaiz Houria Boulaiz |
author_sort |
Alberto Ramírez |
title |
Enhancement of Tumor Cell Death by Combining gef Gene Mediated Therapy and New 1,4-Benzoxazepin-2,6-Dichloropurine Derivatives in Breast Cancer Cells |
title_short |
Enhancement of Tumor Cell Death by Combining gef Gene Mediated Therapy and New 1,4-Benzoxazepin-2,6-Dichloropurine Derivatives in Breast Cancer Cells |
title_full |
Enhancement of Tumor Cell Death by Combining gef Gene Mediated Therapy and New 1,4-Benzoxazepin-2,6-Dichloropurine Derivatives in Breast Cancer Cells |
title_fullStr |
Enhancement of Tumor Cell Death by Combining gef Gene Mediated Therapy and New 1,4-Benzoxazepin-2,6-Dichloropurine Derivatives in Breast Cancer Cells |
title_full_unstemmed |
Enhancement of Tumor Cell Death by Combining gef Gene Mediated Therapy and New 1,4-Benzoxazepin-2,6-Dichloropurine Derivatives in Breast Cancer Cells |
title_sort |
enhancement of tumor cell death by combining gef gene mediated therapy and new 1,4-benzoxazepin-2,6-dichloropurine derivatives in breast cancer cells |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Pharmacology |
issn |
1663-9812 |
publishDate |
2018-07-01 |
description |
New treatment modalities are urgently needed to better manage advanced breast cancer. Combination therapies are usually more effective than monotherapy. In this context, the use of cyclic and acyclic O,N-acetals derivative compounds in combination with the suicide gef gene shown a potent anti-tumor activity and represent a new generation of anticancer agents. Here, we evaluate the use of the gef gene to promote and increase the anti-tumor effect of cyclic and acyclic O,N-acetals purine derivatives and elucidate their mechanisms of action. Among all compounds tested, those with a nitro group and a cyclic pattern structures (FC-30b2, FC-29c, and bozepinib) are the most benefited from the gef gene effect. These compounds, in combination with gef gene, were able to abolish tumor cell proliferation with a minimal dose leading to more effective and less toxic chemotherapy. The effect of this combined therapy is triggered by apoptosis induction which can be found deregulated in the later stage of breast cancer. Moreover, the combined therapy leads to an increase of cell post-apoptotic secondary necrosis that is able to promote the immunogenicity of cancer cells leading to a successful treatment. This data suggests that this novel combination therapy represents a promising candidate for breast cancer treatment. |
topic |
gef gene 1 4-benzoxazepin-2 6-dichloropurine breast cancer combined therapy |
url |
https://www.frontiersin.org/article/10.3389/fphar.2018.00798/full |
work_keys_str_mv |
AT albertoramirez enhancementoftumorcelldeathbycombininggefgenemediatedtherapyandnew14benzoxazepin26dichloropurinederivativesinbreastcancercells AT albertoramirez enhancementoftumorcelldeathbycombininggefgenemediatedtherapyandnew14benzoxazepin26dichloropurinederivativesinbreastcancercells AT anaconejogarcia enhancementoftumorcelldeathbycombininggefgenemediatedtherapyandnew14benzoxazepin26dichloropurinederivativesinbreastcancercells AT carmengrinanlison enhancementoftumorcelldeathbycombininggefgenemediatedtherapyandnew14benzoxazepin26dichloropurinederivativesinbreastcancercells AT carmengrinanlison enhancementoftumorcelldeathbycombininggefgenemediatedtherapyandnew14benzoxazepin26dichloropurinederivativesinbreastcancercells AT carmengrinanlison enhancementoftumorcelldeathbycombininggefgenemediatedtherapyandnew14benzoxazepin26dichloropurinederivativesinbreastcancercells AT luisaclopezcara enhancementoftumorcelldeathbycombininggefgenemediatedtherapyandnew14benzoxazepin26dichloropurinederivativesinbreastcancercells AT gemajimenez enhancementoftumorcelldeathbycombininggefgenemediatedtherapyandnew14benzoxazepin26dichloropurinederivativesinbreastcancercells AT gemajimenez enhancementoftumorcelldeathbycombininggefgenemediatedtherapyandnew14benzoxazepin26dichloropurinederivativesinbreastcancercells AT gemajimenez enhancementoftumorcelldeathbycombininggefgenemediatedtherapyandnew14benzoxazepin26dichloropurinederivativesinbreastcancercells AT joaquinmcampos enhancementoftumorcelldeathbycombininggefgenemediatedtherapyandnew14benzoxazepin26dichloropurinederivativesinbreastcancercells AT juanamarchal enhancementoftumorcelldeathbycombininggefgenemediatedtherapyandnew14benzoxazepin26dichloropurinederivativesinbreastcancercells AT juanamarchal enhancementoftumorcelldeathbycombininggefgenemediatedtherapyandnew14benzoxazepin26dichloropurinederivativesinbreastcancercells AT juanamarchal enhancementoftumorcelldeathbycombininggefgenemediatedtherapyandnew14benzoxazepin26dichloropurinederivativesinbreastcancercells AT houriaboulaiz enhancementoftumorcelldeathbycombininggefgenemediatedtherapyandnew14benzoxazepin26dichloropurinederivativesinbreastcancercells AT houriaboulaiz enhancementoftumorcelldeathbycombininggefgenemediatedtherapyandnew14benzoxazepin26dichloropurinederivativesinbreastcancercells AT houriaboulaiz enhancementoftumorcelldeathbycombininggefgenemediatedtherapyandnew14benzoxazepin26dichloropurinederivativesinbreastcancercells |
_version_ |
1725604100636147712 |