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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....
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2021
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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. |
format | Online Article Text |
id | pubmed-8486119 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
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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