The Role of Aryl Hydrocarbon Receptor and Crosstalk with Estrogen Receptor in Response of Breast Cancer Cells to the Novel Antitumor Agents Benzothiazoles and Aminoflavone

Many estrogen-receptor- (ER-) expressing breast cancers become refractory to ER-based therapies. New antitumor drugs like aminoflavone (AF) and benzothiazoles (Bzs) have been developed and have exquisite antitumor activity in ER+MCF-7 and T47D cells and in a MCF-7 nude mouse model. ER(−) breast canc...

Full description

Saved in:
Bibliographic Details
Main Authors: Mariana A. Callero, Andrea I. Loaiza-Pérez
Format: Article
Language:English
Published: Wiley 2011-01-01
Series:International Journal of Breast Cancer
Online Access:http://dx.doi.org/10.4061/2011/923250
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1850220758507192320
author Mariana A. Callero
Andrea I. Loaiza-Pérez
author_facet Mariana A. Callero
Andrea I. Loaiza-Pérez
author_sort Mariana A. Callero
collection DOAJ
description Many estrogen-receptor- (ER-) expressing breast cancers become refractory to ER-based therapies. New antitumor drugs like aminoflavone (AF) and benzothiazoles (Bzs) have been developed and have exquisite antitumor activity in ER+MCF-7 and T47D cells and in a MCF-7 nude mouse model. ER(−) breast cancer cells like MDA-MB-231 are less susceptible. We previously found in MCF-7 cells that these drugs activate the aryl hydrocarbon receptor (AhR) via translocation to the nucleus, induction of AhR-specific DNA binding activity, and expression of CYP1A1, whose transcription is controlled by the AhR-ARNT transcription factor. CYP1A1 metabolizes AF and Bz to a species which directly or after further metabolism damages DNA. In contrast an AhR-deficient variant of MCF-7 or cells with predominantly nuclear AhR expression, such as MDA-MB 231, are resistant. Thus, these drugs, unlike other neoplastic agents, require AhR-mediated signaling to cause DNA damage. This is a new treatment strategy for breast cancers with intact AhR signaling.
format Article
id doaj-art-7573c3df05f14543ad8cae8024e3a288
institution OA Journals
issn 2090-3189
language English
publishDate 2011-01-01
publisher Wiley
record_format Article
series International Journal of Breast Cancer
spelling doaj-art-7573c3df05f14543ad8cae8024e3a2882025-08-20T02:06:57ZengWileyInternational Journal of Breast Cancer2090-31892011-01-01201110.4061/2011/923250923250The Role of Aryl Hydrocarbon Receptor and Crosstalk with Estrogen Receptor in Response of Breast Cancer Cells to the Novel Antitumor Agents Benzothiazoles and AminoflavoneMariana A. Callero0Andrea I. Loaiza-Pérez1Research Area, Institute of Oncology “Ángel H. Roffo”, University of Buenos Aires, Avenue San Martín 5481, C1417DTB Ciudad de Buenos Aires, ArgentinaResearch Area, Institute of Oncology “Ángel H. Roffo”, University of Buenos Aires, Avenue San Martín 5481, C1417DTB Ciudad de Buenos Aires, ArgentinaMany estrogen-receptor- (ER-) expressing breast cancers become refractory to ER-based therapies. New antitumor drugs like aminoflavone (AF) and benzothiazoles (Bzs) have been developed and have exquisite antitumor activity in ER+MCF-7 and T47D cells and in a MCF-7 nude mouse model. ER(−) breast cancer cells like MDA-MB-231 are less susceptible. We previously found in MCF-7 cells that these drugs activate the aryl hydrocarbon receptor (AhR) via translocation to the nucleus, induction of AhR-specific DNA binding activity, and expression of CYP1A1, whose transcription is controlled by the AhR-ARNT transcription factor. CYP1A1 metabolizes AF and Bz to a species which directly or after further metabolism damages DNA. In contrast an AhR-deficient variant of MCF-7 or cells with predominantly nuclear AhR expression, such as MDA-MB 231, are resistant. Thus, these drugs, unlike other neoplastic agents, require AhR-mediated signaling to cause DNA damage. This is a new treatment strategy for breast cancers with intact AhR signaling.http://dx.doi.org/10.4061/2011/923250
spellingShingle Mariana A. Callero
Andrea I. Loaiza-Pérez
The Role of Aryl Hydrocarbon Receptor and Crosstalk with Estrogen Receptor in Response of Breast Cancer Cells to the Novel Antitumor Agents Benzothiazoles and Aminoflavone
International Journal of Breast Cancer
title The Role of Aryl Hydrocarbon Receptor and Crosstalk with Estrogen Receptor in Response of Breast Cancer Cells to the Novel Antitumor Agents Benzothiazoles and Aminoflavone
title_full The Role of Aryl Hydrocarbon Receptor and Crosstalk with Estrogen Receptor in Response of Breast Cancer Cells to the Novel Antitumor Agents Benzothiazoles and Aminoflavone
title_fullStr The Role of Aryl Hydrocarbon Receptor and Crosstalk with Estrogen Receptor in Response of Breast Cancer Cells to the Novel Antitumor Agents Benzothiazoles and Aminoflavone
title_full_unstemmed The Role of Aryl Hydrocarbon Receptor and Crosstalk with Estrogen Receptor in Response of Breast Cancer Cells to the Novel Antitumor Agents Benzothiazoles and Aminoflavone
title_short The Role of Aryl Hydrocarbon Receptor and Crosstalk with Estrogen Receptor in Response of Breast Cancer Cells to the Novel Antitumor Agents Benzothiazoles and Aminoflavone
title_sort role of aryl hydrocarbon receptor and crosstalk with estrogen receptor in response of breast cancer cells to the novel antitumor agents benzothiazoles and aminoflavone
url http://dx.doi.org/10.4061/2011/923250
work_keys_str_mv AT marianaacallero theroleofarylhydrocarbonreceptorandcrosstalkwithestrogenreceptorinresponseofbreastcancercellstothenovelantitumoragentsbenzothiazolesandaminoflavone
AT andreailoaizaperez theroleofarylhydrocarbonreceptorandcrosstalkwithestrogenreceptorinresponseofbreastcancercellstothenovelantitumoragentsbenzothiazolesandaminoflavone
AT marianaacallero roleofarylhydrocarbonreceptorandcrosstalkwithestrogenreceptorinresponseofbreastcancercellstothenovelantitumoragentsbenzothiazolesandaminoflavone
AT andreailoaizaperez roleofarylhydrocarbonreceptorandcrosstalkwithestrogenreceptorinresponseofbreastcancercellstothenovelantitumoragentsbenzothiazolesandaminoflavone