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Potent cytotoxicity and induction of ROS-mediated genomic instability, mitochondrial dysfunction, and apoptosis by
Hanan R H Mohamed1, Rawan Essam2, Basma A Mohamed2
1Department of Zoology, Faculty of Science, Cairo University, Giza, Egypt. hananeeyra@cu.edu.eg.
Abstract:
Hepatic cancer, one of the most prevalent and lethal cancers globally, remains a significant health challenge, with limited treatment options underscoring the urgent need for novel, more effective therapies. Yttrium oxide nanoparticles (Y2O3 NPs) have attracted attention in nanomedicine due to their promising properties, including enhanced drug delivery, imaging capabilities, and therapeutic effects. However, the specific impact of Y2O3 NPs on hepatic cancer is largely unexplored. Therefore, this study was conducted to assess the cytotoxic effects of Y2O3 NPs on cell viability, reactive oxygen species (ROS) generation, genomic stability, mitochondrial integrity, and apoptosis induction in Hep-G2 hepatic cancer cells. The results from the SRB cytotoxicity assay demonstrated a strong concentration-dependent decrease in Hep-G2 cell viability, with a notably low half-maximal inhibitory concentration (IC50) value of 13.15 µg/ml. Exposure to the IC50 concentration of Y2O3 NPs led to increased ROS generation, DNA damage induction, and loss of mitochondrial membrane potential. Furthermore, the expression of pro-apoptotic p53 and mitochondrial ND3 genes was significantly upregulated, while the anti-apoptotic Bcl-2 gene was markedly downregulated, triggering apoptosis in Hep-G2 cells after 72 h of exposure to Y2O3 NPs. Collectively, these findings highlight the therapeutic potential of Y2O3 NPs in hepatic cancer, emphasizing the need for further research to fully explore their efficacy as a treatment option for liver cancer.
Insights
Yttrium oxide nanoparticles (Y2O3 NPs) show significant potential for treating liver cancer by inducing cancer cell death. Further research is needed to explore Y2O3 NPs as a novel therapeutic option for hepatic cancer.
Area of Science:
- Nanomedicine
- Oncology
- Materials Science
Background:
- Hepatic cancer is a major global health concern with limited effective treatments.
- Yttrium oxide nanoparticles (Y2O3 NPs) offer potential in nanomedicine for drug delivery and therapy.
- The therapeutic effects of Y2O3 NPs on hepatic cancer cells are not well understood.
Purpose of the Study:
- To investigate the cytotoxic effects of Y2O3 NPs on Hep-G2 hepatic cancer cells.
- To evaluate the impact of Y2O3 NPs on cell viability, reactive oxygen species (ROS) generation, genomic stability, mitochondrial integrity, and apoptosis.
- To determine the potential of Y2O3 NPs as a novel therapeutic agent for liver cancer.
Main Methods:
- Sulforhodamine B (SRB) cytotoxicity assay to determine cell viability and IC50.
- Assessment of reactive oxygen species (ROS) generation.
- Evaluation of DNA damage, mitochondrial membrane potential, and apoptosis-related gene expression (p53, ND3, Bcl-2).
Main Results:
- Y2O3 NPs exhibited a concentration-dependent decrease in Hep-G2 cell viability with an IC50 of 13.15 µg/ml.
- Exposure to Y2O3 NPs at the IC50 concentration increased ROS generation, induced DNA damage, and disrupted mitochondrial membrane potential.
- Y2O3 NPs upregulated pro-apoptotic genes (p53, ND3) and downregulated anti-apoptotic gene (Bcl-2), triggering apoptosis in Hep-G2 cells.
Conclusions:
- Yttrium oxide nanoparticles demonstrate significant cytotoxic effects on hepatic cancer cells.
- Y2O3 NPs induce apoptosis in Hep-G2 cells through ROS generation, DNA damage, and mitochondrial pathway.
- These findings suggest Y2O3 NPs hold therapeutic promise for liver cancer treatment, warranting further investigation.
