Doxorubicin–transferrin conjugate alters mitochondrial homeostasis and energy metabolism in human breast cancer cells

Abstract Doxorubicin (DOX) is considered one of the most powerful chemotherapeutic agents but its clinical use has several limitations, including cardiomyopathy and cellular resistance to the drug. By using transferrin (Tf) as a drug carrier, however, the adverse effects of doxorubicin as well as dr...

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Autores principales:	Paulina Wigner, Krzysztof Zielinski, Magdalena Labieniec-Watala, Agnieszka Marczak, Marzena Szwed
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/b33adf26b2264bd79ed3bafd26548ba8
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spelling	oai:doaj.org-article:b33adf26b2264bd79ed3bafd26548ba82021-12-02T13:34:33ZDoxorubicin–transferrin conjugate alters mitochondrial homeostasis and energy metabolism in human breast cancer cells10.1038/s41598-021-84146-42045-2322https://doaj.org/article/b33adf26b2264bd79ed3bafd26548ba82021-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-84146-4https://doaj.org/toc/2045-2322Abstract Doxorubicin (DOX) is considered one of the most powerful chemotherapeutic agents but its clinical use has several limitations, including cardiomyopathy and cellular resistance to the drug. By using transferrin (Tf) as a drug carrier, however, the adverse effects of doxorubicin as well as drug resistance can be reduced. The main objective of this study was to determine the exact nature and extent to which mitochondrial function is influenced by DOX–Tf conjugate treatment, specifically in human breast adenocarcinoma cells. We assessed the potential of DOX–Tf conjugate as a drug delivery system, monitoring its cytotoxicity using the MTT assay and ATP measurements. Moreover, we measured the alterations of mitochondrial function and oxidative stress markers. The effect of DOX–Tf was the most pronounced in MDA-MB-231, triple-negative breast cancer cells, whereas non-cancer endothelial HUVEC-ST cells were more resistant to DOX–Tf conjugate than to free DOX treatment. A different sensitivity of two investigate breast cancer cell lines corresponded to the functionality of their cellular antioxidant systems and expression of estrogen receptors. Our data also revealed that conjugate treatment mediated free radical generation and altered the mitochondrial bioenergetics in breast cancer cells.Paulina WignerKrzysztof ZielinskiMagdalena Labieniec-WatalaAgnieszka MarczakMarzena SzwedNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Paulina Wigner Krzysztof Zielinski Magdalena Labieniec-Watala Agnieszka Marczak Marzena Szwed Doxorubicin–transferrin conjugate alters mitochondrial homeostasis and energy metabolism in human breast cancer cells
description	Abstract Doxorubicin (DOX) is considered one of the most powerful chemotherapeutic agents but its clinical use has several limitations, including cardiomyopathy and cellular resistance to the drug. By using transferrin (Tf) as a drug carrier, however, the adverse effects of doxorubicin as well as drug resistance can be reduced. The main objective of this study was to determine the exact nature and extent to which mitochondrial function is influenced by DOX–Tf conjugate treatment, specifically in human breast adenocarcinoma cells. We assessed the potential of DOX–Tf conjugate as a drug delivery system, monitoring its cytotoxicity using the MTT assay and ATP measurements. Moreover, we measured the alterations of mitochondrial function and oxidative stress markers. The effect of DOX–Tf was the most pronounced in MDA-MB-231, triple-negative breast cancer cells, whereas non-cancer endothelial HUVEC-ST cells were more resistant to DOX–Tf conjugate than to free DOX treatment. A different sensitivity of two investigate breast cancer cell lines corresponded to the functionality of their cellular antioxidant systems and expression of estrogen receptors. Our data also revealed that conjugate treatment mediated free radical generation and altered the mitochondrial bioenergetics in breast cancer cells.
format	article
author	Paulina Wigner Krzysztof Zielinski Magdalena Labieniec-Watala Agnieszka Marczak Marzena Szwed
author_facet	Paulina Wigner Krzysztof Zielinski Magdalena Labieniec-Watala Agnieszka Marczak Marzena Szwed
author_sort	Paulina Wigner
title	Doxorubicin–transferrin conjugate alters mitochondrial homeostasis and energy metabolism in human breast cancer cells
title_short	Doxorubicin–transferrin conjugate alters mitochondrial homeostasis and energy metabolism in human breast cancer cells
title_full	Doxorubicin–transferrin conjugate alters mitochondrial homeostasis and energy metabolism in human breast cancer cells
title_fullStr	Doxorubicin–transferrin conjugate alters mitochondrial homeostasis and energy metabolism in human breast cancer cells
title_full_unstemmed	Doxorubicin–transferrin conjugate alters mitochondrial homeostasis and energy metabolism in human breast cancer cells
title_sort	doxorubicin–transferrin conjugate alters mitochondrial homeostasis and energy metabolism in human breast cancer cells
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/b33adf26b2264bd79ed3bafd26548ba8
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Doxorubicin–transferrin conjugate alters mitochondrial homeostasis and energy metabolism in human breast cancer cells

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