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Effects of N-Acetylcysteine and Alpha-Ketoglutarate on OVCAR3 Ovarian Cancer Cells: Insights from Integrative
Yasaman Khamineh1, Sanaz Panahi-Alanagh1, Samaneh Zolghadri2
1Department of Animal Sciences and Marine Biology, Faculty of Life Sciences and Biotechnology, Shahid Beheshti University, Tehran 1983969411, Iran.
Abstract:
Ovarian cancer remains one of the leading causes of cancer-related mortality among women, underscoring the need for novel combination strategies that effectively inhibit tumor cell growth while limiting adverse effects. N-acetylcysteine (NAC) and alpha-ketoglutarate (AKG) are biologically active compounds with reported anticancer properties; however, their combined effects in ovarian cancer are not well characterized. In this study, we applied an integrative approach combining network pharmacology analysis with in vitro experiments to investigate the effects of NAC and AKG on OVCAR3 ovarian cancer cells. Common molecular targets of NAC and AKG were identified by intersecting predicted compound targets with ovarian cancer-associated genes, followed by protein-protein interaction network construction and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses. Experimental validation assessed the effects of NAC and AKG, alone and in combination, on cell viability, apoptosis, migration, and clonogenic capacity. Network analysis identified 70 shared target genes enriched in pathways related to apoptosis, cellular stress responses, and cell migration. In vitro experiments demonstrated that combined treatment with NAC (10 mM) and AKG (100 µM) significantly reduced cell viability, increased apoptotic cell death, and markedly suppressed cell migration and colony formation compared with single-agent treatments. Overall, these findings indicate that the combination of NAC and AKG exerts enhanced inhibitory effects on ovarian cancer cell growth and motility in vitro.
Insights
N-acetylcysteine (NAC) and alpha-ketoglutarate (AKG) combination therapy shows promise for ovarian cancer treatment. This study found that combining NAC and AKG significantly inhibits ovarian cancer cell growth, migration, and colony formation in vitro.
Area of Science:
- Oncology
- Pharmacology
- Molecular Biology
Background:
- Ovarian cancer is a leading cause of cancer mortality in women, necessitating innovative combination therapies.
- N-acetylcysteine (NAC) and alpha-ketoglutarate (AKG) possess anticancer properties, but their combined efficacy in ovarian cancer is not well understood.
Purpose of the Study:
- To investigate the synergistic effects of NAC and AKG on ovarian cancer cells using an integrative network pharmacology and in vitro approach.
- To identify common molecular targets and pathways affected by NAC and AKG in ovarian cancer.
Main Methods:
- Network pharmacology analysis to identify shared targets between NAC, AKG, and ovarian cancer genes.
- Protein-protein interaction network construction and pathway enrichment analysis (GO, KEGG).
- In vitro validation of combined NAC and AKG effects on OVCAR3 cell viability, apoptosis, migration, and clonogenic capacity.
Main Results:
- Network analysis revealed 70 shared target genes involved in apoptosis, cellular stress, and cell migration pathways.
- Combined NAC (10 mM) and AKG (100 µM) treatment significantly reduced OVCAR3 cell viability.
- Combination therapy markedly suppressed ovarian cancer cell migration and colony formation compared to single agents.
Conclusions:
- The combination of NAC and AKG demonstrates enhanced inhibitory effects on ovarian cancer cell growth and motility.
- This synergistic effect suggests potential for a novel therapeutic strategy against ovarian cancer.
- Further research into the molecular mechanisms underlying NAC and AKG synergy is warranted.
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