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Induction of mitochondria mediated apoptosis in human ovarian cancer cells by folic acid coated tin oxide nanoparticles

PURPOSE: This study aims to prepare folic acid coated tin oxide nanoparticles (FA-SnO(2) NPs) for specifically targeting human ovarian cancer cells with minimum side effects against normal cells. METHODS: The prepared FA-SnO(2) NPs were characterized by FT-IR, UV-vis spectroscopy, XRD, SEM and TEM....

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Autores principales: Hanna, Demiana H., R. Saad, Gamal
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8486119/
https://www.ncbi.nlm.nih.gov/pubmed/34597348
http://dx.doi.org/10.1371/journal.pone.0258115
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author Hanna, Demiana H.
R. Saad, Gamal
author_facet Hanna, Demiana H.
R. Saad, Gamal
author_sort Hanna, Demiana H.
collection PubMed
description PURPOSE: This study aims to prepare folic acid coated tin oxide nanoparticles (FA-SnO(2) NPs) for specifically targeting human ovarian cancer cells with minimum side effects against normal cells. METHODS: The prepared FA-SnO(2) NPs were characterized by FT-IR, UV-vis spectroscopy, XRD, SEM and TEM. The inhibition effects of FA-SnO(2) NPs against SKOV3 cancer cell were tested by MTT and LDH assay. Apoptosis induction in FA-SnO(2) NPs treated SKOV3 cells were investigated using Annexin V/PI, AO/EB and Comet assays and the possible mechanisms of the cytotoxic action were studied by Flow cytometry, qRT-PCR, Immunohistochemistry, and Western blotting analyses. The effects of FA-SnO(2) NPs on reactive oxygen species generation in SKOV3 cells were also examined. Additionally, the safety of utilization FA-SnO(2) NPs were studied in vivo using Wister rats. RESULTS: The obtained FA-SnO(2) NPs displayed amorphous spherical morphology with an average diameter of 157 nm and a zeta potential value of -24 mV. Comparing to uncoated SnO(2) NPs, FA-SnO(2) NPs had a superior inhibition effect towards SKOV3 cell growth that was suggested to be mediated through higher reactive oxygen species generation. It was showed that FA-SnO(2) NPs increased significantly the % of apoptotic cells in the sub- G1 and G2/M phases with a higher intensity comet nucleus in SKOV3 treated cells. Furthermore, FA-SnO(2) NPs was significantly increased the expression levels of P53, Bax, and cleaved Caspase-3 and accompanied with a significant decrease of Bcl-2 in the treated SKOV3 cells. CONCLUSION: Overall, the results suggested that an increase in cellular FA-SnO(2) NPs internalization resulted in a significant induced cytotoxicity in SKOV3 cancer cells in dose-dependent mode through ROS-mediated cell apoptosis that may have occurred through mitochondrial pathway. Additionally, the results confirmed the safety of utilization FA-SnO(2) NPs against living systems. So, FA-SnO(2) NPs with a specific targeting moiety may be a promising therapeutic candidate for human ovarian cancer.
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spelling pubmed-84861192021-10-02 Induction of mitochondria mediated apoptosis in human ovarian cancer cells by folic acid coated tin oxide nanoparticles Hanna, Demiana H. R. Saad, Gamal PLoS One Research Article PURPOSE: This study aims to prepare folic acid coated tin oxide nanoparticles (FA-SnO(2) NPs) for specifically targeting human ovarian cancer cells with minimum side effects against normal cells. METHODS: The prepared FA-SnO(2) NPs were characterized by FT-IR, UV-vis spectroscopy, XRD, SEM and TEM. The inhibition effects of FA-SnO(2) NPs against SKOV3 cancer cell were tested by MTT and LDH assay. Apoptosis induction in FA-SnO(2) NPs treated SKOV3 cells were investigated using Annexin V/PI, AO/EB and Comet assays and the possible mechanisms of the cytotoxic action were studied by Flow cytometry, qRT-PCR, Immunohistochemistry, and Western blotting analyses. The effects of FA-SnO(2) NPs on reactive oxygen species generation in SKOV3 cells were also examined. Additionally, the safety of utilization FA-SnO(2) NPs were studied in vivo using Wister rats. RESULTS: The obtained FA-SnO(2) NPs displayed amorphous spherical morphology with an average diameter of 157 nm and a zeta potential value of -24 mV. Comparing to uncoated SnO(2) NPs, FA-SnO(2) NPs had a superior inhibition effect towards SKOV3 cell growth that was suggested to be mediated through higher reactive oxygen species generation. It was showed that FA-SnO(2) NPs increased significantly the % of apoptotic cells in the sub- G1 and G2/M phases with a higher intensity comet nucleus in SKOV3 treated cells. Furthermore, FA-SnO(2) NPs was significantly increased the expression levels of P53, Bax, and cleaved Caspase-3 and accompanied with a significant decrease of Bcl-2 in the treated SKOV3 cells. CONCLUSION: Overall, the results suggested that an increase in cellular FA-SnO(2) NPs internalization resulted in a significant induced cytotoxicity in SKOV3 cancer cells in dose-dependent mode through ROS-mediated cell apoptosis that may have occurred through mitochondrial pathway. Additionally, the results confirmed the safety of utilization FA-SnO(2) NPs against living systems. So, FA-SnO(2) NPs with a specific targeting moiety may be a promising therapeutic candidate for human ovarian cancer. Public Library of Science 2021-10-01 /pmc/articles/PMC8486119/ /pubmed/34597348 http://dx.doi.org/10.1371/journal.pone.0258115 Text en © 2021 Hanna, R. Saad https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Hanna, Demiana H.
R. Saad, Gamal
Induction of mitochondria mediated apoptosis in human ovarian cancer cells by folic acid coated tin oxide nanoparticles
title Induction of mitochondria mediated apoptosis in human ovarian cancer cells by folic acid coated tin oxide nanoparticles
title_full Induction of mitochondria mediated apoptosis in human ovarian cancer cells by folic acid coated tin oxide nanoparticles
title_fullStr Induction of mitochondria mediated apoptosis in human ovarian cancer cells by folic acid coated tin oxide nanoparticles
title_full_unstemmed Induction of mitochondria mediated apoptosis in human ovarian cancer cells by folic acid coated tin oxide nanoparticles
title_short Induction of mitochondria mediated apoptosis in human ovarian cancer cells by folic acid coated tin oxide nanoparticles
title_sort induction of mitochondria mediated apoptosis in human ovarian cancer cells by folic acid coated tin oxide nanoparticles
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8486119/
https://www.ncbi.nlm.nih.gov/pubmed/34597348
http://dx.doi.org/10.1371/journal.pone.0258115
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