Journal Article

Cobalt oxide nanoparticles induce cytotoxicity and excessive ROS mediated mitochondrial dysfunction and p53-independent apoptosis in melanoma cells

Mohamed, Basma A., Diab, Ayman, Elnawasani, Shahd H., Essam, Rawan, Safwat, Gehan, Hakeem, George M., Nagy, Maria, Mohamed, Hanan R. H.

2025

Overview

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 (Co 3 O 4 NPs) in melanoma treatment remains unexplored. This study aimed to assess the therapeutic potential of Co 3 O 4 NPs 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 Co 3 O 4 NP 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 Co 3 O 4 NP 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 Co 3 O 4 NPs 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 Co 3 O 4 NPs as a promising nanotherapeutic candidate for melanoma treatment, warranting further exploration to elucidate their full biological and clinical applicability.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 631/208 / 631/326 / 692/308 / 692/700 / Apoptosis / Apoptosis - drug effects / Bcl-2 protein / Cancer / Cell death / Cell Line, Tumor / Cell Survival - drug effects / Cell viability / Co3O4NPs / Cobalt / Cobalt - chemistry / Cobalt - pharmacology / Cytotoxicity / Deoxyribonucleic acid / DNA / DNA damage / DNA Damage - drug effects / Flow cytometry / Gene expression / Genes / Genomic instability / Humanities and Social Sciences / Humans / Melanoma / Melanoma - drug therapy / Melanoma - metabolism / Melanoma - pathology / Melanoma A-375 cells / Membrane potential / Membrane Potential, Mitochondrial - drug effects / Metal Nanoparticles - chemistry / Mitochondria - drug effects / Mitochondria - metabolism / Mitochondrial DNA / Mitochondrial dysfunction / multidisciplinary / Nanoparticles / Nanoparticles - chemistry / Oxidative DNA damage / Oxides - chemistry / Oxides - pharmacology / p53 independent apoptosis / p53 Protein / Reactive oxygen species / Reactive Oxygen Species - metabolism / Science / Science (multidisciplinary) / Skin cancer / Tumor Suppressor Protein p53 - genetics / Tumor Suppressor Protein p53 - metabolism