Connexin-43 enhances tumor suppressing activity of artesunate via gap junction-dependent as well as independent pathways in human breast cancer cells

Abstract The gap junction (GJ) protein connexin-43 (Cx43) is considered as a tumour suppressor protein for its role in reversing the phenotype of the cancer cells. In this study, we exploited the antitumor property of Cx43 in conjunction with the artesunate (ART), a plant-based active anti-malarial...

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Autores principales:	Asif Raza, Archita Ghoshal, S. Chockalingam, Siddhartha Sankar Ghosh
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/18312af788fa441992ba482539b4c824
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spelling	oai:doaj.org-article:18312af788fa441992ba482539b4c8242021-12-02T12:32:14ZConnexin-43 enhances tumor suppressing activity of artesunate via gap junction-dependent as well as independent pathways in human breast cancer cells10.1038/s41598-017-08058-y2045-2322https://doaj.org/article/18312af788fa441992ba482539b4c8242017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-08058-yhttps://doaj.org/toc/2045-2322Abstract The gap junction (GJ) protein connexin-43 (Cx43) is considered as a tumour suppressor protein for its role in reversing the phenotype of the cancer cells. In this study, we exploited the antitumor property of Cx43 in conjunction with the artesunate (ART), a plant-based active anti-malarial compound. The reactive oxygen species (ROS) generated by ART resulted in DNA damage, which in turn led to DNA damage response by activation of DNA damage repair proteins. GJ deficient MCF-7 cells transfected with Cx43 gene showed an increased sensitivity towards dose-dependent ART treatment and required a significantly lower dose of ART to attain its IC50, as compared to parental cells. This would ultimately result in reduced dose-dependent side effects of ART. The Co-culture experiments involving GJ intercellular communication (GJIC) deficient and GJIC enabled cells, established the transfer of ROS to the neighbouring cancer cells not exposed to ART. The ROS accumulated in the ART-treated cells induced the oxidative damage in neighbouring cells, leading to bystander cell death and inhibition of bystander cell proliferation. Thus, our study revealed that expression of Cx43 helped in reducing the dose-dependent cytotoxicity of ART as well as enhanced the bystander apoptosis of the neighbouring cells.Asif RazaArchita GhoshalS. ChockalingamSiddhartha Sankar GhoshNature 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 Asif Raza Archita Ghoshal S. Chockalingam Siddhartha Sankar Ghosh Connexin-43 enhances tumor suppressing activity of artesunate via gap junction-dependent as well as independent pathways in human breast cancer cells
description	Abstract The gap junction (GJ) protein connexin-43 (Cx43) is considered as a tumour suppressor protein for its role in reversing the phenotype of the cancer cells. In this study, we exploited the antitumor property of Cx43 in conjunction with the artesunate (ART), a plant-based active anti-malarial compound. The reactive oxygen species (ROS) generated by ART resulted in DNA damage, which in turn led to DNA damage response by activation of DNA damage repair proteins. GJ deficient MCF-7 cells transfected with Cx43 gene showed an increased sensitivity towards dose-dependent ART treatment and required a significantly lower dose of ART to attain its IC50, as compared to parental cells. This would ultimately result in reduced dose-dependent side effects of ART. The Co-culture experiments involving GJ intercellular communication (GJIC) deficient and GJIC enabled cells, established the transfer of ROS to the neighbouring cancer cells not exposed to ART. The ROS accumulated in the ART-treated cells induced the oxidative damage in neighbouring cells, leading to bystander cell death and inhibition of bystander cell proliferation. Thus, our study revealed that expression of Cx43 helped in reducing the dose-dependent cytotoxicity of ART as well as enhanced the bystander apoptosis of the neighbouring cells.
format	article
author	Asif Raza Archita Ghoshal S. Chockalingam Siddhartha Sankar Ghosh
author_facet	Asif Raza Archita Ghoshal S. Chockalingam Siddhartha Sankar Ghosh
author_sort	Asif Raza
title	Connexin-43 enhances tumor suppressing activity of artesunate via gap junction-dependent as well as independent pathways in human breast cancer cells
title_short	Connexin-43 enhances tumor suppressing activity of artesunate via gap junction-dependent as well as independent pathways in human breast cancer cells
title_full	Connexin-43 enhances tumor suppressing activity of artesunate via gap junction-dependent as well as independent pathways in human breast cancer cells
title_fullStr	Connexin-43 enhances tumor suppressing activity of artesunate via gap junction-dependent as well as independent pathways in human breast cancer cells
title_full_unstemmed	Connexin-43 enhances tumor suppressing activity of artesunate via gap junction-dependent as well as independent pathways in human breast cancer cells
title_sort	connexin-43 enhances tumor suppressing activity of artesunate via gap junction-dependent as well as independent pathways in human breast cancer cells
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/18312af788fa441992ba482539b4c824
work_keys_str_mv	AT asifraza connexin43enhancestumorsuppressingactivityofartesunateviagapjunctiondependentaswellasindependentpathwaysinhumanbreastcancercells AT architaghoshal connexin43enhancestumorsuppressingactivityofartesunateviagapjunctiondependentaswellasindependentpathwaysinhumanbreastcancercells AT schockalingam connexin43enhancestumorsuppressingactivityofartesunateviagapjunctiondependentaswellasindependentpathwaysinhumanbreastcancercells AT siddharthasankarghosh connexin43enhancestumorsuppressingactivityofartesunateviagapjunctiondependentaswellasindependentpathwaysinhumanbreastcancercells
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Connexin-43 enhances tumor suppressing activity of artesunate via gap junction-dependent as well as independent pathways in human breast cancer cells

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