Vitamin D-Mediated Anti-cancer Activity Involves Iron Homeostatic Balance Disruption and Oxidative Stress Induction in Breast Cancer

Background: Vitamin D deficiency associates with high risk of breast cancer (BRCA) and increased cellular iron. Vitamin D exerts some of its anti-cancer effects by regulating the expression of key iron regulatory genes (IRGs). The association between vitamin D and cellular iron content in BRCA remai...

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Autores principales:	Khuloud Bajbouj, Lina Sahnoon, Jasmin Shafarin, Abeer Al-Ali, Jibran Sualeh Muhammad, Asima Karim, Salman Y. Guraya, Mawieh Hamad
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	vitamin D breast cancer iron oxidative stress cell death Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/50e3aa6185e142359180d42a2a164a62
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spelling	oai:doaj.org-article:50e3aa6185e142359180d42a2a164a622021-11-08T08:07:24ZVitamin D-Mediated Anti-cancer Activity Involves Iron Homeostatic Balance Disruption and Oxidative Stress Induction in Breast Cancer2296-634X10.3389/fcell.2021.766978https://doaj.org/article/50e3aa6185e142359180d42a2a164a622021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fcell.2021.766978/fullhttps://doaj.org/toc/2296-634XBackground: Vitamin D deficiency associates with high risk of breast cancer (BRCA) and increased cellular iron. Vitamin D exerts some of its anti-cancer effects by regulating the expression of key iron regulatory genes (IRGs). The association between vitamin D and cellular iron content in BRCA remains ambiguous. Herein, we addressed whether vitamin D signaling exerts a role in cellular iron homeostasis thereby affecting survival of breast cancer cells.Methods: Expression profile of IRGs in vitamin D-treated breast cancer cells was analyzed using publicly available transcriptomic datasets. After treatment of BRCA cell lines MCF-7 and MDA-MB-231 with the active form of vitamin D, labile iron content, IRGs protein levels, oxidative stress, and cell survival were evaluated.Results: Bioinformatics analysis revealed several IRGs as well as cellular stress relates genes were differentially expressed in BRCA cells. Vitamin D treatment resulted in cellular iron depletion and differentially affected the expression of key IRGs protein levels. Vitamin D treatment exerted oxidative stress induction and alteration in the cellular redox balance by increasing the synthesis of key stress-related markers. Collectively, these effects resulted in a significant decrease in BRCA cell survival.Conclusion: These findings suggest that vitamin D disrupts cellular iron homeostasis leading to oxidative stress induction and cell death.Khuloud BajboujKhuloud BajboujLina SahnoonJasmin ShafarinAbeer Al-AliJibran Sualeh MuhammadJibran Sualeh MuhammadAsima KarimAsima KarimSalman Y. GurayaSalman Y. GurayaMawieh HamadMawieh HamadFrontiers Media S.A.articlevitamin Dbreast cancerironoxidative stresscell deathBiology (General)QH301-705.5ENFrontiers in Cell and Developmental Biology, Vol 9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	vitamin D breast cancer iron oxidative stress cell death Biology (General) QH301-705.5
spellingShingle	vitamin D breast cancer iron oxidative stress cell death Biology (General) QH301-705.5 Khuloud Bajbouj Khuloud Bajbouj Lina Sahnoon Jasmin Shafarin Abeer Al-Ali Jibran Sualeh Muhammad Jibran Sualeh Muhammad Asima Karim Asima Karim Salman Y. Guraya Salman Y. Guraya Mawieh Hamad Mawieh Hamad Vitamin D-Mediated Anti-cancer Activity Involves Iron Homeostatic Balance Disruption and Oxidative Stress Induction in Breast Cancer
description	Background: Vitamin D deficiency associates with high risk of breast cancer (BRCA) and increased cellular iron. Vitamin D exerts some of its anti-cancer effects by regulating the expression of key iron regulatory genes (IRGs). The association between vitamin D and cellular iron content in BRCA remains ambiguous. Herein, we addressed whether vitamin D signaling exerts a role in cellular iron homeostasis thereby affecting survival of breast cancer cells.Methods: Expression profile of IRGs in vitamin D-treated breast cancer cells was analyzed using publicly available transcriptomic datasets. After treatment of BRCA cell lines MCF-7 and MDA-MB-231 with the active form of vitamin D, labile iron content, IRGs protein levels, oxidative stress, and cell survival were evaluated.Results: Bioinformatics analysis revealed several IRGs as well as cellular stress relates genes were differentially expressed in BRCA cells. Vitamin D treatment resulted in cellular iron depletion and differentially affected the expression of key IRGs protein levels. Vitamin D treatment exerted oxidative stress induction and alteration in the cellular redox balance by increasing the synthesis of key stress-related markers. Collectively, these effects resulted in a significant decrease in BRCA cell survival.Conclusion: These findings suggest that vitamin D disrupts cellular iron homeostasis leading to oxidative stress induction and cell death.
format	article
author	Khuloud Bajbouj Khuloud Bajbouj Lina Sahnoon Jasmin Shafarin Abeer Al-Ali Jibran Sualeh Muhammad Jibran Sualeh Muhammad Asima Karim Asima Karim Salman Y. Guraya Salman Y. Guraya Mawieh Hamad Mawieh Hamad
author_facet	Khuloud Bajbouj Khuloud Bajbouj Lina Sahnoon Jasmin Shafarin Abeer Al-Ali Jibran Sualeh Muhammad Jibran Sualeh Muhammad Asima Karim Asima Karim Salman Y. Guraya Salman Y. Guraya Mawieh Hamad Mawieh Hamad
author_sort	Khuloud Bajbouj
title	Vitamin D-Mediated Anti-cancer Activity Involves Iron Homeostatic Balance Disruption and Oxidative Stress Induction in Breast Cancer
title_short	Vitamin D-Mediated Anti-cancer Activity Involves Iron Homeostatic Balance Disruption and Oxidative Stress Induction in Breast Cancer
title_full	Vitamin D-Mediated Anti-cancer Activity Involves Iron Homeostatic Balance Disruption and Oxidative Stress Induction in Breast Cancer
title_fullStr	Vitamin D-Mediated Anti-cancer Activity Involves Iron Homeostatic Balance Disruption and Oxidative Stress Induction in Breast Cancer
title_full_unstemmed	Vitamin D-Mediated Anti-cancer Activity Involves Iron Homeostatic Balance Disruption and Oxidative Stress Induction in Breast Cancer
title_sort	vitamin d-mediated anti-cancer activity involves iron homeostatic balance disruption and oxidative stress induction in breast cancer
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/50e3aa6185e142359180d42a2a164a62
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Vitamin D-Mediated Anti-cancer Activity Involves Iron Homeostatic Balance Disruption and Oxidative Stress Induction in Breast Cancer

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