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Yttrium Oxide nanoparticles induce cytotoxicity, genotoxicity, apoptosis, and ferroptosis in the human triple-negative breast cancer MDA-MB-231 cells

BACKGROUND: Triple-negative breast cancer (TNBC) is a lethal mammary carcinoma subtype that affects females and is associated with a worse prognosis. Chemotherapy is the only conventional therapy available for patients with TNBC due to the lack of therapeutic targets. Yttrium oxide (Y(2)O(3)) is a r...

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Autores principales: Emad, Basant, WalyEldeen, Amr Ahmed, Hassan, Hebatallah, Sharaky, Marwa, Abdelhamid, Ismail A, Ibrahim, Sherif Abdelaziz, Mohamed, Hanan RH
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10680179/
https://www.ncbi.nlm.nih.gov/pubmed/38012585
http://dx.doi.org/10.1186/s12885-023-11649-w
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author Emad, Basant
WalyEldeen, Amr Ahmed
Hassan, Hebatallah
Sharaky, Marwa
Abdelhamid, Ismail A
Ibrahim, Sherif Abdelaziz
Mohamed, Hanan RH
author_facet Emad, Basant
WalyEldeen, Amr Ahmed
Hassan, Hebatallah
Sharaky, Marwa
Abdelhamid, Ismail A
Ibrahim, Sherif Abdelaziz
Mohamed, Hanan RH
author_sort Emad, Basant
collection PubMed
description BACKGROUND: Triple-negative breast cancer (TNBC) is a lethal mammary carcinoma subtype that affects females and is associated with a worse prognosis. Chemotherapy is the only conventional therapy available for patients with TNBC due to the lack of therapeutic targets. Yttrium oxide (Y(2)O(3)) is a rare earth metal oxide, whose nanoparticle (NPs) formulations are used in various applications, including biological imaging, the material sciences, and the chemical synthesis of inorganic chemicals. However, the biological activity of Y(2)O(3)-NPs against TNBC cells has not been fully explored. The current study was conducted to assess Y(2)O(3)-NPs’ anticancer activity against the human TNBC MDA-MB-231 cell line. METHODS: Transmission electron microscopy (TEM), X-ray diffraction, Zeta potential, and dynamic light scattering (DLS) were used to characterize the Y(2)O(3)-NPs. SRB cell viability, reactive oxygen species (ROS) measurement, single-cell gel electrophoresis (comet assay), qPCR, flow cytometry, and Western blot were employed to assess the anticancer activity of the Y(2)O(3)-NPs. RESULTS: Our results indicate favorable physiochemical properties of Y(2)O(3)-NPs (with approximately average size 14 nm, Zeta Potential about − 53.2 mV, and polydispersity index = 0.630). Y(2)O(3)-NPs showed a potent cytotoxic effect against MDA-MB-231 cells, with IC50 values of 74.4 µg/mL, without cytotoxic effect on the normal retina REP1 and human dermal fibroblast HDF cell lines. Further, treatment of MDA-MB-231 cells with IC50 Y(2)O(3)-NPs resulted in increased oxidative stress, accumulation of intracellular ROS levels, and induced DNA damage assessed by Comet assay. Upon Y(2)O(3)-NPs treatment, a significant increase in the early and late phases of apoptosis was revealed in MDA-MB-231 cells. qPCR results showed that Y(2)O(3)-NPs significantly upregulated the pro-apoptotic genes CASP3 and CASP8 as well as ferroptosis-related gene heme oxygenase-1 (HO-1), whereas the anti-apoptotic gene BCL2 was significantly downregulated. CONCLUSION: This study suggests that Y(2)O(3)-NPs are safe on normal REP1 and HDF cells and exhibited a potent selective cytotoxic effect against the TNBC MDA-MB-231 cells through increasing levels of ROS generation with subsequent DNA damage, and induction of apoptosis and ferroptosis. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12885-023-11649-w.
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spelling pubmed-106801792023-11-27 Yttrium Oxide nanoparticles induce cytotoxicity, genotoxicity, apoptosis, and ferroptosis in the human triple-negative breast cancer MDA-MB-231 cells Emad, Basant WalyEldeen, Amr Ahmed Hassan, Hebatallah Sharaky, Marwa Abdelhamid, Ismail A Ibrahim, Sherif Abdelaziz Mohamed, Hanan RH BMC Cancer Research BACKGROUND: Triple-negative breast cancer (TNBC) is a lethal mammary carcinoma subtype that affects females and is associated with a worse prognosis. Chemotherapy is the only conventional therapy available for patients with TNBC due to the lack of therapeutic targets. Yttrium oxide (Y(2)O(3)) is a rare earth metal oxide, whose nanoparticle (NPs) formulations are used in various applications, including biological imaging, the material sciences, and the chemical synthesis of inorganic chemicals. However, the biological activity of Y(2)O(3)-NPs against TNBC cells has not been fully explored. The current study was conducted to assess Y(2)O(3)-NPs’ anticancer activity against the human TNBC MDA-MB-231 cell line. METHODS: Transmission electron microscopy (TEM), X-ray diffraction, Zeta potential, and dynamic light scattering (DLS) were used to characterize the Y(2)O(3)-NPs. SRB cell viability, reactive oxygen species (ROS) measurement, single-cell gel electrophoresis (comet assay), qPCR, flow cytometry, and Western blot were employed to assess the anticancer activity of the Y(2)O(3)-NPs. RESULTS: Our results indicate favorable physiochemical properties of Y(2)O(3)-NPs (with approximately average size 14 nm, Zeta Potential about − 53.2 mV, and polydispersity index = 0.630). Y(2)O(3)-NPs showed a potent cytotoxic effect against MDA-MB-231 cells, with IC50 values of 74.4 µg/mL, without cytotoxic effect on the normal retina REP1 and human dermal fibroblast HDF cell lines. Further, treatment of MDA-MB-231 cells with IC50 Y(2)O(3)-NPs resulted in increased oxidative stress, accumulation of intracellular ROS levels, and induced DNA damage assessed by Comet assay. Upon Y(2)O(3)-NPs treatment, a significant increase in the early and late phases of apoptosis was revealed in MDA-MB-231 cells. qPCR results showed that Y(2)O(3)-NPs significantly upregulated the pro-apoptotic genes CASP3 and CASP8 as well as ferroptosis-related gene heme oxygenase-1 (HO-1), whereas the anti-apoptotic gene BCL2 was significantly downregulated. CONCLUSION: This study suggests that Y(2)O(3)-NPs are safe on normal REP1 and HDF cells and exhibited a potent selective cytotoxic effect against the TNBC MDA-MB-231 cells through increasing levels of ROS generation with subsequent DNA damage, and induction of apoptosis and ferroptosis. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12885-023-11649-w. BioMed Central 2023-11-27 /pmc/articles/PMC10680179/ /pubmed/38012585 http://dx.doi.org/10.1186/s12885-023-11649-w Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Emad, Basant
WalyEldeen, Amr Ahmed
Hassan, Hebatallah
Sharaky, Marwa
Abdelhamid, Ismail A
Ibrahim, Sherif Abdelaziz
Mohamed, Hanan RH
Yttrium Oxide nanoparticles induce cytotoxicity, genotoxicity, apoptosis, and ferroptosis in the human triple-negative breast cancer MDA-MB-231 cells
title Yttrium Oxide nanoparticles induce cytotoxicity, genotoxicity, apoptosis, and ferroptosis in the human triple-negative breast cancer MDA-MB-231 cells
title_full Yttrium Oxide nanoparticles induce cytotoxicity, genotoxicity, apoptosis, and ferroptosis in the human triple-negative breast cancer MDA-MB-231 cells
title_fullStr Yttrium Oxide nanoparticles induce cytotoxicity, genotoxicity, apoptosis, and ferroptosis in the human triple-negative breast cancer MDA-MB-231 cells
title_full_unstemmed Yttrium Oxide nanoparticles induce cytotoxicity, genotoxicity, apoptosis, and ferroptosis in the human triple-negative breast cancer MDA-MB-231 cells
title_short Yttrium Oxide nanoparticles induce cytotoxicity, genotoxicity, apoptosis, and ferroptosis in the human triple-negative breast cancer MDA-MB-231 cells
title_sort yttrium oxide nanoparticles induce cytotoxicity, genotoxicity, apoptosis, and ferroptosis in the human triple-negative breast cancer mda-mb-231 cells
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10680179/
https://www.ncbi.nlm.nih.gov/pubmed/38012585
http://dx.doi.org/10.1186/s12885-023-11649-w
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