Y2O3NPs induce selective cytotoxicity, genomic instability, oxidative stress and ROS mediated mitochondrial apoptosis in human epidermoid skin A-431 Cancer cells
Abstract Yttrium oxide nanoparticles (Y2O3NPs) have emerged as a promising avenue for cancer therapy, primarily due to their distinctive properties that facilitate selective targeting of cancer cells. Despite their potential, the therapeutic effects of Y2O3NPs on human epidermoid skin cancer remain...
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Nature Portfolio
2025-01-01
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| Online Access: | https://doi.org/10.1038/s41598-024-82376-w |
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| author | Hanan RH Mohamed Shrouk H.A Hemdan Ahmed A. El-Sherif |
| author_facet | Hanan RH Mohamed Shrouk H.A Hemdan Ahmed A. El-Sherif |
| author_sort | Hanan RH Mohamed |
| collection | DOAJ |
| description | Abstract Yttrium oxide nanoparticles (Y2O3NPs) have emerged as a promising avenue for cancer therapy, primarily due to their distinctive properties that facilitate selective targeting of cancer cells. Despite their potential, the therapeutic effects of Y2O3NPs on human epidermoid skin cancer remain largely unexplored. This study was thus conducted to investigate the impact of Y2O3NPs on both human skin normal and cancer cells, with an emphasis on assessing their cytotoxicity, genotoxicity, and the mechanisms underlying these effects. Cell viability and apoptosis induction were assessed using the Sulforhodamine B and chromatin diffusion assay, respectively. Reactive oxygen species (ROS) level, mitochondrial membrane potential integrity, oxidative stress markers and expression level of apoptotic and mitochondrial genes were also estimated. Our findings highlight the selective and significant cytotoxicity of Y2O3NPs against human epidermoid A-431 cancer cells. Notably, exposure to five Y2O3NPs concentrations (0.1, 1, 10, 100 and 1000 µg/ml) resulted in a high concentration-dependent reduction in cell viability and a corresponding increase in cell death observed 72 h post-treatment specifically in A-431 cancer cells, while normal skin fibroblast (HSF) cells exhibited minimal toxicity. When A-431 cancer cells were treated with the half-maximal inhibitory concentration (IC50) of Y2O3NPs for 72 h, a significant increase in ROS generation was noted. This led to oxidative stress, along with severe damage to genomic DNA and mitochondrial membrane potential, triggering substantial apoptosis. Furthermore, a concurrent significant upregulation of apoptotic p53 and mitochondrial ND3 genes was observed, coupled with a notable decrease in the anti-apoptotic Bcl2 gene expression. Overall, Y2O3NPs demonstrate considerable promise as a therapeutic agent for skin epidermoid cancer due to their ability to selectively target and induce cytotoxic effects in A-431 cancer cells, all while causing minimal harm to normal HSF cells. This selective cytotoxicity appears to be associated with Y2O3NPs’ ability to induce excessive ROS production and subsequent oxidative stress, leading to significant genomic DNA fragmentation, loss of mitochondrial permeability, and alterations in apoptotic and mitochondrial genes’ expression, ultimately promoting apoptosis in A-431 cancer cells. These findings establish a foundation for further research into the utilization of Y2O3NPs in targeted cancer therapies and underscore the necessity for ongoing investigation into their safety and efficacy in clinical applications. |
| format | Article |
| id | doaj-art-273ca60005c64e97b8e7b139891e41b0 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
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| series | Scientific Reports |
| spelling | doaj-art-273ca60005c64e97b8e7b139891e41b02025-01-12T12:22:03ZengNature PortfolioScientific Reports2045-23222025-01-0115111510.1038/s41598-024-82376-wY2O3NPs induce selective cytotoxicity, genomic instability, oxidative stress and ROS mediated mitochondrial apoptosis in human epidermoid skin A-431 Cancer cellsHanan RH Mohamed0Shrouk H.A Hemdan1Ahmed A. El-Sherif2Department of Zoology, Faculty of Science, Cairo UniversityDepartment of Zoology, Faculty of Science, Cairo UniversityDepartment of Chemistry, Faculty of Science, Cairo UniversityAbstract Yttrium oxide nanoparticles (Y2O3NPs) have emerged as a promising avenue for cancer therapy, primarily due to their distinctive properties that facilitate selective targeting of cancer cells. Despite their potential, the therapeutic effects of Y2O3NPs on human epidermoid skin cancer remain largely unexplored. This study was thus conducted to investigate the impact of Y2O3NPs on both human skin normal and cancer cells, with an emphasis on assessing their cytotoxicity, genotoxicity, and the mechanisms underlying these effects. Cell viability and apoptosis induction were assessed using the Sulforhodamine B and chromatin diffusion assay, respectively. Reactive oxygen species (ROS) level, mitochondrial membrane potential integrity, oxidative stress markers and expression level of apoptotic and mitochondrial genes were also estimated. Our findings highlight the selective and significant cytotoxicity of Y2O3NPs against human epidermoid A-431 cancer cells. Notably, exposure to five Y2O3NPs concentrations (0.1, 1, 10, 100 and 1000 µg/ml) resulted in a high concentration-dependent reduction in cell viability and a corresponding increase in cell death observed 72 h post-treatment specifically in A-431 cancer cells, while normal skin fibroblast (HSF) cells exhibited minimal toxicity. When A-431 cancer cells were treated with the half-maximal inhibitory concentration (IC50) of Y2O3NPs for 72 h, a significant increase in ROS generation was noted. This led to oxidative stress, along with severe damage to genomic DNA and mitochondrial membrane potential, triggering substantial apoptosis. Furthermore, a concurrent significant upregulation of apoptotic p53 and mitochondrial ND3 genes was observed, coupled with a notable decrease in the anti-apoptotic Bcl2 gene expression. Overall, Y2O3NPs demonstrate considerable promise as a therapeutic agent for skin epidermoid cancer due to their ability to selectively target and induce cytotoxic effects in A-431 cancer cells, all while causing minimal harm to normal HSF cells. This selective cytotoxicity appears to be associated with Y2O3NPs’ ability to induce excessive ROS production and subsequent oxidative stress, leading to significant genomic DNA fragmentation, loss of mitochondrial permeability, and alterations in apoptotic and mitochondrial genes’ expression, ultimately promoting apoptosis in A-431 cancer cells. These findings establish a foundation for further research into the utilization of Y2O3NPs in targeted cancer therapies and underscore the necessity for ongoing investigation into their safety and efficacy in clinical applications.https://doi.org/10.1038/s41598-024-82376-wYttrium oxide nanoparticlesCytotoxicity, genotoxicity, apoptosisOxidative stress and mitochondria |
| spellingShingle | Hanan RH Mohamed Shrouk H.A Hemdan Ahmed A. El-Sherif Y2O3NPs induce selective cytotoxicity, genomic instability, oxidative stress and ROS mediated mitochondrial apoptosis in human epidermoid skin A-431 Cancer cells Scientific Reports Yttrium oxide nanoparticles Cytotoxicity, genotoxicity, apoptosis Oxidative stress and mitochondria |
| title | Y2O3NPs induce selective cytotoxicity, genomic instability, oxidative stress and ROS mediated mitochondrial apoptosis in human epidermoid skin A-431 Cancer cells |
| title_full | Y2O3NPs induce selective cytotoxicity, genomic instability, oxidative stress and ROS mediated mitochondrial apoptosis in human epidermoid skin A-431 Cancer cells |
| title_fullStr | Y2O3NPs induce selective cytotoxicity, genomic instability, oxidative stress and ROS mediated mitochondrial apoptosis in human epidermoid skin A-431 Cancer cells |
| title_full_unstemmed | Y2O3NPs induce selective cytotoxicity, genomic instability, oxidative stress and ROS mediated mitochondrial apoptosis in human epidermoid skin A-431 Cancer cells |
| title_short | Y2O3NPs induce selective cytotoxicity, genomic instability, oxidative stress and ROS mediated mitochondrial apoptosis in human epidermoid skin A-431 Cancer cells |
| title_sort | y2o3nps induce selective cytotoxicity genomic instability oxidative stress and ros mediated mitochondrial apoptosis in human epidermoid skin a 431 cancer cells |
| topic | Yttrium oxide nanoparticles Cytotoxicity, genotoxicity, apoptosis Oxidative stress and mitochondria |
| url | https://doi.org/10.1038/s41598-024-82376-w |
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