Cobalt oxide nanoparticles induce cytotoxicity and excessive ROS mediated mitochondrial dysfunction and p53-independent apoptosis in melanoma cells
Abstract Nanotherapy has emerged as a promising strategy for the targeted and efficient treatment of melanoma, the most aggressive and lethal form of skin cancer, with minimized systemic toxicity. However, the therapeutic efficacy of cobalt oxide nanoparticles (Co3O4NPs) in melanoma treatment remain...
Saved in:
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-01-01
|
| Series: | Scientific Reports |
| Subjects: | |
| Online Access: | https://doi.org/10.1038/s41598-025-85691-y |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832594803631587328 |
|---|---|
| author | Hanan R. H. Mohamed Basma A. Mohamed George M. Hakeem Shahd H. Elnawasani Maria Nagy Rawan Essam Ayman Diab Gehan Safwat |
| author_facet | Hanan R. H. Mohamed Basma A. Mohamed George M. Hakeem Shahd H. Elnawasani Maria Nagy Rawan Essam Ayman Diab Gehan Safwat |
| author_sort | Hanan R. H. Mohamed |
| collection | DOAJ |
| description | Abstract Nanotherapy has emerged as a promising strategy for the targeted and efficient treatment of melanoma, the most aggressive and lethal form of skin cancer, with minimized systemic toxicity. However, the therapeutic efficacy of cobalt oxide nanoparticles (Co3O4NPs) in melanoma treatment remains unexplored. This study aimed to assess the therapeutic potential of Co3O4NPs in melanoma treatment by evaluating their impact on cell viability, genomic DNA and mitochondrial integrity, reactive oxygen species (ROS) generation and apoptosis induction in melanoma A-375 cells. Our findings demonstrated a concentration-dependent reduction in cell viability upon treatment with five Co3O4NP concentrations (0.2, 2, 20, 200, and 2000 µg/ml), with an IC50 value of 303.80 µg/ml. Treatment with this IC50 concentration significantly increased ROS generation, induced dramatic DNA damage, and disrupted mitochondrial membrane potential integrity. Flow cytometric analysis revealed apoptosis and necrosis induction following Co3O4NP exposure at the IC50 concentration value. Results of qRT-PCR analysis demonstrated remarkable dysregulation of apoptotic and mitochondrial genes, including a significant downregulation of apoptotic p53 and mitochondrial ND3 genes and marked upregulation of the anti-apoptotic gene Bcl2. These findings highlight the novel potential of Co3O4NPs as potent inducers of melanoma A-375 cell death in a concentration-dependent manner through excessive ROS production, genomic instability, mitochondrial dysfunction and dysregulation of apoptotic and mitochondrial gene expression, ultimately promoting apoptosis in A-375 cells. This study thus underscores the potential of Co3O4NPs as a promising nanotherapeutic candidate for melanoma treatment, warranting further exploration to elucidate their full biological and clinical applicability. |
| format | Article |
| id | doaj-art-fc17ac1f81fa449ea3d131926678884e |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-fc17ac1f81fa449ea3d131926678884e2025-01-19T12:22:47ZengNature PortfolioScientific Reports2045-23222025-01-0115111210.1038/s41598-025-85691-yCobalt oxide nanoparticles induce cytotoxicity and excessive ROS mediated mitochondrial dysfunction and p53-independent apoptosis in melanoma cellsHanan R. H. Mohamed0Basma A. Mohamed1George M. Hakeem2Shahd H. Elnawasani3Maria Nagy4Rawan Essam5Ayman Diab6Gehan Safwat7Department of Zoology, Faculty of Science, Cairo UniversityFaculty of Biotechnology, October University for Modern Sciences and Arts (MSA)Faculty of Biotechnology, October University for Modern Sciences and Arts (MSA)Faculty of Biotechnology, October University for Modern Sciences and Arts (MSA)Faculty of Biotechnology, October University for Modern Sciences and Arts (MSA)Faculty of Biotechnology, October University for Modern Sciences and Arts (MSA)Faculty of Biotechnology, October University for Modern Sciences and Arts (MSA)Faculty of Biotechnology, October University for Modern Sciences and Arts (MSA)Abstract Nanotherapy has emerged as a promising strategy for the targeted and efficient treatment of melanoma, the most aggressive and lethal form of skin cancer, with minimized systemic toxicity. However, the therapeutic efficacy of cobalt oxide nanoparticles (Co3O4NPs) in melanoma treatment remains unexplored. This study aimed to assess the therapeutic potential of Co3O4NPs in melanoma treatment by evaluating their impact on cell viability, genomic DNA and mitochondrial integrity, reactive oxygen species (ROS) generation and apoptosis induction in melanoma A-375 cells. Our findings demonstrated a concentration-dependent reduction in cell viability upon treatment with five Co3O4NP concentrations (0.2, 2, 20, 200, and 2000 µg/ml), with an IC50 value of 303.80 µg/ml. Treatment with this IC50 concentration significantly increased ROS generation, induced dramatic DNA damage, and disrupted mitochondrial membrane potential integrity. Flow cytometric analysis revealed apoptosis and necrosis induction following Co3O4NP exposure at the IC50 concentration value. Results of qRT-PCR analysis demonstrated remarkable dysregulation of apoptotic and mitochondrial genes, including a significant downregulation of apoptotic p53 and mitochondrial ND3 genes and marked upregulation of the anti-apoptotic gene Bcl2. These findings highlight the novel potential of Co3O4NPs as potent inducers of melanoma A-375 cell death in a concentration-dependent manner through excessive ROS production, genomic instability, mitochondrial dysfunction and dysregulation of apoptotic and mitochondrial gene expression, ultimately promoting apoptosis in A-375 cells. This study thus underscores the potential of Co3O4NPs as a promising nanotherapeutic candidate for melanoma treatment, warranting further exploration to elucidate their full biological and clinical applicability.https://doi.org/10.1038/s41598-025-85691-yCo3O4NPsMelanoma A-375 cellsOxidative DNA damageMitochondrial dysfunctionp53 independent apoptosis |
| spellingShingle | Hanan R. H. Mohamed Basma A. Mohamed George M. Hakeem Shahd H. Elnawasani Maria Nagy Rawan Essam Ayman Diab Gehan Safwat Cobalt oxide nanoparticles induce cytotoxicity and excessive ROS mediated mitochondrial dysfunction and p53-independent apoptosis in melanoma cells Scientific Reports Co3O4NPs Melanoma A-375 cells Oxidative DNA damage Mitochondrial dysfunction p53 independent apoptosis |
| title | Cobalt oxide nanoparticles induce cytotoxicity and excessive ROS mediated mitochondrial dysfunction and p53-independent apoptosis in melanoma cells |
| title_full | Cobalt oxide nanoparticles induce cytotoxicity and excessive ROS mediated mitochondrial dysfunction and p53-independent apoptosis in melanoma cells |
| title_fullStr | Cobalt oxide nanoparticles induce cytotoxicity and excessive ROS mediated mitochondrial dysfunction and p53-independent apoptosis in melanoma cells |
| title_full_unstemmed | Cobalt oxide nanoparticles induce cytotoxicity and excessive ROS mediated mitochondrial dysfunction and p53-independent apoptosis in melanoma cells |
| title_short | Cobalt oxide nanoparticles induce cytotoxicity and excessive ROS mediated mitochondrial dysfunction and p53-independent apoptosis in melanoma cells |
| title_sort | cobalt oxide nanoparticles induce cytotoxicity and excessive ros mediated mitochondrial dysfunction and p53 independent apoptosis in melanoma cells |
| topic | Co3O4NPs Melanoma A-375 cells Oxidative DNA damage Mitochondrial dysfunction p53 independent apoptosis |
| url | https://doi.org/10.1038/s41598-025-85691-y |
| work_keys_str_mv | AT hananrhmohamed cobaltoxidenanoparticlesinducecytotoxicityandexcessiverosmediatedmitochondrialdysfunctionandp53independentapoptosisinmelanomacells AT basmaamohamed cobaltoxidenanoparticlesinducecytotoxicityandexcessiverosmediatedmitochondrialdysfunctionandp53independentapoptosisinmelanomacells AT georgemhakeem cobaltoxidenanoparticlesinducecytotoxicityandexcessiverosmediatedmitochondrialdysfunctionandp53independentapoptosisinmelanomacells AT shahdhelnawasani cobaltoxidenanoparticlesinducecytotoxicityandexcessiverosmediatedmitochondrialdysfunctionandp53independentapoptosisinmelanomacells AT marianagy cobaltoxidenanoparticlesinducecytotoxicityandexcessiverosmediatedmitochondrialdysfunctionandp53independentapoptosisinmelanomacells AT rawanessam cobaltoxidenanoparticlesinducecytotoxicityandexcessiverosmediatedmitochondrialdysfunctionandp53independentapoptosisinmelanomacells AT aymandiab cobaltoxidenanoparticlesinducecytotoxicityandexcessiverosmediatedmitochondrialdysfunctionandp53independentapoptosisinmelanomacells AT gehansafwat cobaltoxidenanoparticlesinducecytotoxicityandexcessiverosmediatedmitochondrialdysfunctionandp53independentapoptosisinmelanomacells |