In vivo and in vitro studies evaluating the chemopreventive effect of metformin on the aryl hydrocarbon receptor-mediated breast carcinogenesis

Metformin (MET) is a clinically used anti-hyperglycemic agent that shows activities against chemically-induced animal models of cancer. A study from our laboratory showed that MET protectes against 7, 12-dimethylbenz[a]anthracene (DMBA)-induced carcinogenesis in vitro human non-cancerous epithelial...

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Autores principales:	Ali Alhoshani, Moureq Alotaibi, Homood M. As Sobeai, Naif Alharbi, Khalid Alhazzani, Abdullah Al-Dhfyan, Fawaz E. Alanazi, Hesham M. Korashy
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Metformin Breast carcinogenesis DMBA AhR Mammosphere Apoptosis Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/ba1ec5258f5640a192f407e5338df709
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spelling	oai:doaj.org-article:ba1ec5258f5640a192f407e5338df7092021-11-20T04:57:10ZIn vivo and in vitro studies evaluating the chemopreventive effect of metformin on the aryl hydrocarbon receptor-mediated breast carcinogenesis1319-562X10.1016/j.sjbs.2021.08.051https://doaj.org/article/ba1ec5258f5640a192f407e5338df7092021-12-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S1319562X21007403https://doaj.org/toc/1319-562XMetformin (MET) is a clinically used anti-hyperglycemic agent that shows activities against chemically-induced animal models of cancer. A study from our laboratory showed that MET protectes against 7, 12-dimethylbenz[a]anthracene (DMBA)-induced carcinogenesis in vitro human non-cancerous epithelial breast cells (MCF10A) via activation of the aryl hydrocarbon receptor (AhR). However, it is unclear whether MET can prevent the initiation of breast carcinogenesis in an in vivo rat model of AhR-induced breast carcinogenesis. Therefore, the main aims of this study are to examine the effect of MET on protecting against rat breast carcinogenesis induced by DMBA and to explore whether this effect is medicated through the AhR pathway. In this study, treatment of female rats with DMBA initiated breast carcinogenesis though inhibiting apoptosis and tumor suppressor genes while inducing oxidative DNA damage and cell cycle proliferative markers. This effect was associated with activation of AhR and its downstream target genes; cytochrome P4501A1 (CYP1A1) and CYP1B1. Importantly, MET treatment protected against DMBA-induced breast carcinogenesis by restoring DMBA effects on apoptosis, tumor suppressor genes, DNA damage, and cell proliferation. Mechanistically using in vitro human breast cancer MCF-7 cells, MET inhibited breast cancer stem cells spheroids formation and development by DMBA, which was accompanied by a proportional inhibition in CYP1A1 gene expression. In conclusion, the study reports evidence that MET is an effective chemopreventive therapy for breast cancer by inhibiting the activation of CYP1A1/CYP1B1 pathway in vivo rat model.Ali AlhoshaniMoureq AlotaibiHomood M. As SobeaiNaif AlharbiKhalid AlhazzaniAbdullah Al-DhfyanFawaz E. AlanaziHesham M. KorashyElsevierarticleMetforminBreast carcinogenesisDMBAAhRMammosphereApoptosisBiology (General)QH301-705.5ENSaudi Journal of Biological Sciences, Vol 28, Iss 12, Pp 7396-7403 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Metformin Breast carcinogenesis DMBA AhR Mammosphere Apoptosis Biology (General) QH301-705.5
spellingShingle	Metformin Breast carcinogenesis DMBA AhR Mammosphere Apoptosis Biology (General) QH301-705.5 Ali Alhoshani Moureq Alotaibi Homood M. As Sobeai Naif Alharbi Khalid Alhazzani Abdullah Al-Dhfyan Fawaz E. Alanazi Hesham M. Korashy In vivo and in vitro studies evaluating the chemopreventive effect of metformin on the aryl hydrocarbon receptor-mediated breast carcinogenesis
description	Metformin (MET) is a clinically used anti-hyperglycemic agent that shows activities against chemically-induced animal models of cancer. A study from our laboratory showed that MET protectes against 7, 12-dimethylbenz[a]anthracene (DMBA)-induced carcinogenesis in vitro human non-cancerous epithelial breast cells (MCF10A) via activation of the aryl hydrocarbon receptor (AhR). However, it is unclear whether MET can prevent the initiation of breast carcinogenesis in an in vivo rat model of AhR-induced breast carcinogenesis. Therefore, the main aims of this study are to examine the effect of MET on protecting against rat breast carcinogenesis induced by DMBA and to explore whether this effect is medicated through the AhR pathway. In this study, treatment of female rats with DMBA initiated breast carcinogenesis though inhibiting apoptosis and tumor suppressor genes while inducing oxidative DNA damage and cell cycle proliferative markers. This effect was associated with activation of AhR and its downstream target genes; cytochrome P4501A1 (CYP1A1) and CYP1B1. Importantly, MET treatment protected against DMBA-induced breast carcinogenesis by restoring DMBA effects on apoptosis, tumor suppressor genes, DNA damage, and cell proliferation. Mechanistically using in vitro human breast cancer MCF-7 cells, MET inhibited breast cancer stem cells spheroids formation and development by DMBA, which was accompanied by a proportional inhibition in CYP1A1 gene expression. In conclusion, the study reports evidence that MET is an effective chemopreventive therapy for breast cancer by inhibiting the activation of CYP1A1/CYP1B1 pathway in vivo rat model.
format	article
author	Ali Alhoshani Moureq Alotaibi Homood M. As Sobeai Naif Alharbi Khalid Alhazzani Abdullah Al-Dhfyan Fawaz E. Alanazi Hesham M. Korashy
author_facet	Ali Alhoshani Moureq Alotaibi Homood M. As Sobeai Naif Alharbi Khalid Alhazzani Abdullah Al-Dhfyan Fawaz E. Alanazi Hesham M. Korashy
author_sort	Ali Alhoshani
title	In vivo and in vitro studies evaluating the chemopreventive effect of metformin on the aryl hydrocarbon receptor-mediated breast carcinogenesis
title_short	In vivo and in vitro studies evaluating the chemopreventive effect of metformin on the aryl hydrocarbon receptor-mediated breast carcinogenesis
title_full	In vivo and in vitro studies evaluating the chemopreventive effect of metformin on the aryl hydrocarbon receptor-mediated breast carcinogenesis
title_fullStr	In vivo and in vitro studies evaluating the chemopreventive effect of metformin on the aryl hydrocarbon receptor-mediated breast carcinogenesis
title_full_unstemmed	In vivo and in vitro studies evaluating the chemopreventive effect of metformin on the aryl hydrocarbon receptor-mediated breast carcinogenesis
title_sort	in vivo and in vitro studies evaluating the chemopreventive effect of metformin on the aryl hydrocarbon receptor-mediated breast carcinogenesis
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/ba1ec5258f5640a192f407e5338df709
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In vivo and in vitro studies evaluating the chemopreventive effect of metformin on the aryl hydrocarbon receptor-mediated breast carcinogenesis

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