Show simple item record

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

dc.contributor.authorWigner, Paulina
dc.contributor.authorZielinski, Krzysztof
dc.contributor.authorŁabieniec-Watała, Magdalena
dc.contributor.authorMarczak, Agnieszka
dc.contributor.authorSzwed, Marzena
dc.date.accessioned2021-12-16T11:58:43Z
dc.date.available2021-12-16T11:58:43Z
dc.date.issued2021
dc.identifier.citationWigner, P., Zielinski, K., Labieniec-Watala, M. et al. Doxorubicin–transferrin conjugate alters mitochondrial homeostasis and energy metabolism in human breast cancer cells. Sci Rep 11, 4544 (2021). https://doi.org/10.1038/s41598-021-84146-4pl_PL
dc.identifier.urihttp://hdl.handle.net/11089/40077
dc.description.abstractDoxorubicin (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.pl_PL
dc.description.sponsorshipThis work was supported in part by Grant No. B1511000001026.02 of the University of Lodz, Poland.pl_PL
dc.language.isoenpl_PL
dc.publisherSpringer Naturepl_PL
dc.relation.ispartofseriesScientific Reports;11
dc.rightsUznanie autorstwa 4.0 Międzynarodowe*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subjectbiochemistrypl_PL
dc.subjectbiophysicspl_PL
dc.subjectbiotechnologypl_PL
dc.subjectcancerpl_PL
dc.subjectcell biologypl_PL
dc.subjectchemical biologypl_PL
dc.subjectdrug discoverypl_PL
dc.subjectmolecular biologypl_PL
dc.titleDoxorubicin–transferrin conjugate alters mitochondrial homeostasis and energy metabolism in human breast cancer cellspl_PL
dc.typeArticlepl_PL
dc.page.number14pl_PL
dc.contributor.authorAffiliationDepartment of Medical Biophysics, Institute of Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, Lodz, Polandpl_PL
dc.contributor.authorAffiliationDepartment of Medical Biophysics, Institute of Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, Lodz, Polandpl_PL
dc.contributor.authorAffiliationDepartment of Medical Biophysics, Institute of Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, Lodz, Polandpl_PL
dc.contributor.authorAffiliationDepartment of Medical Biophysics, Institute of Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, Lodz, Polandpl_PL
dc.contributor.authorAffiliationDepartment of Medical Biophysics, Institute of Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, Lodz, Polandpl_PL
dc.identifier.eissn2045-2322
dc.referencesJung, M., Mertens, C., Tomat, E. & Brüne, B. Iron as a central player and promising target in cancer progression. Int. J. Mol. Sci. 20, 273. https://doi.org/10.3390/ijms20020273 (2019).pl_PL
dc.referencesMarques, O. et al. Local iron homeostasis in the breast ductal carcinoma microenvironment. BMC Cancer 16, 187–187. https://doi.org/10.1186/s12885-016-2228-y (2016).pl_PL
dc.referencesTorti, S. V. & Torti, F. M. Cellular iron metabolism in prognosis and therapy of breast cancer. Crit. Rev. Oncog. 18, 435–448. https://doi.org/10.1615/critrevoncog.2013007784 (2013).pl_PL
dc.referencesChifman, J. et al. Activated oncogenic pathway modifies iron network in breast epithelial cells: a dynamic modeling perspective. PLoS Comput. Biol. 13, e1005352–e1005352. https://doi.org/10.1371/journal.pcbi.1005352 (2017).pl_PL
dc.referencesMacedo, M. F. et al. Transferrin is required for early T-cell differentiation. Immunology 112, 543–549. https://doi.org/10.1111/j.1365-2567.2004.01915.x (2004).pl_PL
dc.referencesShen, Y. et al. Transferrin receptor 1 in cancer: a new sight for cancer therapy. Am. J. Cancer Res. 8, 916–931 (2018).pl_PL
dc.referencesWrba, F., Ritzinger, E., Reiner, A. & Holzner, J. H. Transferrin receptor (TrfR) expression in breast carcinoma and its possible relationship to prognosis. An immunohistochemical study. Virchows Archiv. A Pathol. Anat. Histopathol. 410, 69–73. https://doi.org/10.1007/bf00710908 (1986).pl_PL
dc.referencesSchulz, D. M. et al. Identification of differentially expressed proteins in triple-negative breast carcinomas using DIGE and mass spectrometry. J. Proteome Res. 8, 3430–3438. https://doi.org/10.1021/pr900071h (2009).pl_PL
dc.referencesWarburg, O. On the origin of cancer cells. Science (New York, N.Y.) 123, 309–314. https://doi.org/10.1126/science.123.3191.309 (1956).pl_PL
dc.referencesDong, L. & Neuzil, J. Targeting mitochondria as an anticancer strategy. Cancer Commun. (London, England) 39, 63. https://doi.org/10.1186/s40880-019-0412-6 (2019).pl_PL
dc.referencesPetrelli, F., Borgonovo, K. & Barni, S. Targeted delivery for breast cancer therapy: the history of nanoparticle-albumin-bound paclitaxel. Expert Opin. Pharmacother. 11, 1413–1432. https://doi.org/10.1517/14656561003796562 (2010).pl_PL
dc.referencesHan, M. et al. Mitochondrial delivery of doxorubicin via triphenylphosphine modification for overcoming drug resistance in MDA-MB-435/DOX cells. Mol. Pharm. 11, 2640–2649. https://doi.org/10.1021/mp500038g (2014).pl_PL
dc.referencesNebigil, C. G. & Désaubry, L. Updates in anthracycline-mediated cardiotoxicity. Front. Pharmacol. 9, 1262. https://doi.org/10.3389/fphar.2018.01262 (2018).pl_PL
dc.referencesSzwed, M. et al. Transferrin as a drug carrier: Cytotoxicity, cellular uptake and transport kinetics of doxorubicin transferrin conjugate in the human leukemia cells. Toxicol. In Vitro 28, 187–197. https://doi.org/10.1016/j.tiv.2013.09.013 (2014).pl_PL
dc.referencesSzwed, M., Wrona, D., Kania, K. D., Koceva-Chyla, A. & Marczak, A. Doxorubicin-transferrin conjugate triggers pro-oxidative disorders in solid tumor cells. Toxicol. In Vitro 31, 60–71. https://doi.org/10.1016/j.tiv.2015.11.009 (2016).pl_PL
dc.referencesJedrzejczyk, M., Wisniewska, K., Kania, K. D., Marczak, A. & Szwed, M. Transferrin-bound doxorubicin enhances apoptosis and DNA damage through the generation of pro-inflammatory responses in human leukemia cells. Int. J. Mol. Sci. 21, 9390. https://doi.org/10.3390/ijms21249390 (2020).pl_PL
dc.referencesHolliday, D. L. & Speirs, V. Choosing the right cell line for breast cancer research. Breast Cancer Res. BCR 13, 215. https://doi.org/10.1186/bcr2889 (2011).pl_PL
dc.referencesCorte-Rodríguez, M., Blanco-González, E., Bettmer, J. & Montes-Bayón, M. Quantitative analysis of Transferrin Receptor 1 (TfR1) in individual breast cancer cells by means of labeled antibodies and elemental (ICP-MS) detection. Anal. Chem. 91, 15532–15538. https://doi.org/10.1021/acs.analchem.9b03438 (2019).pl_PL
dc.referencesHabashy, H. O. et al. Transferrin receptor (CD71) is a marker of poor prognosis in breast cancer and can predict response to tamoxifen. Breast Cancer Res. Treat. 119, 283–293. https://doi.org/10.1007/s10549-009-0345-x (2010).pl_PL
dc.referencesStowe, D. F. & Camara, A. K. Mitochondrial reactive oxygen species production in excitable cells: modulators of mitochondrial and cell function. Antioxid. Redox Signal. 11, 1373–1414. https://doi.org/10.1089/ars.2008.2331 (2009).pl_PL
dc.referencesWang, X., Zhang, H. & Chen, X. Drug resistance and combating drug resistance in cancer. Cancer Drug Resist. 2, 141–160. https://doi.org/10.20517/cdr.2019.10 (2019).pl_PL
dc.referencesYingchoncharoen, P., Kalinowski, D. S. & Richardson, D. R. Lipid-based drug delivery systems in cancer therapy: what is available and what is yet to come. Pharmacol. Rev. 68, 701–787. https://doi.org/10.1124/pr.115.012070 (2016).pl_PL
dc.referencesSenapati, S., Mahanta, A. K., Kumar, S. & Maiti, P. Controlled drug delivery vehicles for cancer treatment and their performance. Signal Transduct. Target Ther. 3, 7–7. https://doi.org/10.1038/s41392-017-0004-3 (2018).pl_PL
dc.referencesAu, J. L. S., Abbiati, R. A., Wientjes, M. G. & Lu, Z. Target site delivery and residence of nanomedicines: application of quantitative systems pharmacology. Pharmacol. Rev. 71, 157–169. https://doi.org/10.1124/pr.118.016816 (2019).pl_PL
dc.referencesFulda, S., Galluzzi, L. & Kroemer, G. Targeting mitochondria for cancer therapy. Nat. Rev. Drug Discov. 9, 447–464. https://doi.org/10.1038/nrd3137 (2010).pl_PL
dc.referencesSzwed, M., Kania, K. D. & Jozwiak, Z. Molecular damage caused by generation of reactive oxygen species in the redox cycle of doxorubicin-transferrin conjugate in human leukemia cell lines. Leukemia Lymphoma 56, 1475–1483. https://doi.org/10.3109/10428194.2014.955022 (2015).pl_PL
dc.referencesTheodossiou, T. A. et al. The diverse roles of glutathione-associated cell resistance against hypericin photodynamic therapy. Redox Biol. 12, 191–197. https://doi.org/10.1016/j.redox.2017.02.018 (2017).pl_PL
dc.referencesSweeney, E. E., Fan, P. & Jordan, V. C. Mechanisms underlying differential response to estrogen-induced apoptosis in long-term estrogen-deprived breast cancer cells. Int. J. Oncol. 44, 1529–1538. https://doi.org/10.3892/ijo.2014.2329 (2014).pl_PL
dc.referencesKayaaltı, Z., Kaya, D., Bacaksız, A., Söylemez, E. & Söylemezoğlu, T. An association between polymorphism of the NADH/NADPH oxidase p22phox (phagocyte oxidase) subunit and aging in Turkish population. Aging Clin. Exp. Res. 25, 511–516. https://doi.org/10.1007/s40520-013-0129-3 (2013).pl_PL
dc.referencesXiong, X. B., Ma, Z., Lai, R. & Lavasanifar, A. The therapeutic response to multifunctional polymeric nano-conjugates in the targeted cellular and subcellular delivery of doxorubicin. Biomaterials 31, 757–768. https://doi.org/10.1016/j.biomaterials.2009.09.080 (2010).pl_PL
dc.referencesBartlett, J. J., Trivedi, P. C. & Pulinilkunnil, T. Autophagic dysregulation in doxorubicin cardiomyopathy. J. Mol. Cell. Cardiol. 104, 1–8. https://doi.org/10.1016/j.yjmcc.2017.01.007 (2017).pl_PL
dc.referencesNeuzil, J., Dong, L. F., Rohlena, J., Truksa, J. & Ralph, S. J. Classification of mitocans, anti-cancer drugs acting on mitochondria. Mitochondrion 13, 199–208. https://doi.org/10.1016/j.mito.2012.07.112 (2013).pl_PL
dc.referencesSuliman, H. B. et al. The CO/HO system reverses inhibition of mitochondrial biogenesis and prevents murine doxorubicin cardiomyopathy. J. Clin. Investig. 117, 3730–3741. https://doi.org/10.1172/JCI32967 (2007).pl_PL
dc.referencesBérczi, A. et al. Influence of conjugation of doxorubicin to transferrin on the iron uptake by K562 cells via receptor-mediated endocytosis. Eur. J. Biochem. 213, 427–436. https://doi.org/10.1111/j.1432-1033.1993.tb17778.x (1993).pl_PL
dc.referencesDowns, T. R. & Wilfinger, W. W. Fluorometric quantification of DNA in cells and tissue. Anal. Biochem. 131, 538–547. https://doi.org/10.1016/0003-2697(83)90212-9 (1983).pl_PL
dc.referencesGnaiger, E. Capacity of oxidative phosphorylation in human skeletal muscle: new perspectives of mitochondrial physiology. Int. J. Biochem. Cell Biol. 41, 1837–1845. https://doi.org/10.1016/j.biocel.2009.03.013 (2009).pl_PL
dc.identifier.doi10.1038/s41598-021-84146-4
dc.relation.volume4544pl_PL
dc.disciplinenauki biologicznepl_PL


Files in this item

Thumbnail
Name:
s41598-021-84146-4.pdf
Size:
4.735Mb
Format:
PDF
Description:
Article
View/Open
Thumbnail
Name:
license_rdf
Size:
908bytes
Format:
application/rdf+xml
View/Open

This item appears in the following Collection(s)

Show simple item record

Uznanie autorstwa 4.0 Międzynarodowe
Except where otherwise noted, this item's license is described as Uznanie autorstwa 4.0 Międzynarodowe