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6-Methoxyflavone targets SLC1A5 to induce ferroptosis in HeLa cells
1Department of Obstetrics and Gynecology, Shaanxi Provincial People's Hospital, Xi'an, Shaanxi, China.
Objective:
This study aimed to explore the role and molecular mechanism of 6-methoxyflavone in inducing ferroptosis in HeLa cells.
Methods:
Transmission electron microscopy (TEM), mitochondrial superoxide, and glutathione content assay were used to detect the effects of 6-methoxyflavone on ferroptosis. Tandem mass tag and parallel reaction monitoring proteomics, non-targeted and targeted metabolomics, polymerase chain reaction (qPCR), western blot, alternative splicing, new transcript, functional domain, molecular docking, non-covalent interaction, loss-of-function genetic manipulation, and mitochondrial superoxide analyses were performed to explore the molecular mechanism of 6-methoxyflavone-induced ferroptosis in HeLa cells.
Results:
6-Methoxyflavone induced ferroptosis in HeLa cells. Multi-omics, qPCR, western blot, alternative splicing, new transcript, functional domain, molecular docking, non-covalent interaction, loss-of-function genetic manipulation, and mitochondrial superoxide analyses indicated that 6-methoxyflavone induced ferroptosis in HeLa cells by upregulating the expression levels of SLC1A5 and mitochondrial superoxide. Molecular docking analyses showed that 6-methoxyflavone had the strongest affinity for SLC1A5. Non-covalent interaction analyses suggested that the interaction between 6-methoxyflavone and SLC1A5 was primarily driven by hydrophobic interactions. 6-Methoxyflavone targeted the peptide segment sequence LGPEGELLIR of SLC1A5.
Conclusion:
6-Methoxyflavone induced ferroptosis in HeLa cells by markedly altering ferroptosis-related genes, proteins, and metabolites expression, thereby exerting anti-cancer effects. The core gene responsible for the induction of ferroptosis and the upregulation of mitochondrial superoxide in HeLa cells by 6-methoxyflavone is SLC1A5.
Insights
6-methoxyflavone triggers ferroptosis in HeLa cells by upregulating SLC1A5 and mitochondrial superoxide. This natural compound shows potential anti-cancer effects by altering key cellular pathways involved in cell death.
Area of Science:
- Cell Biology
- Molecular Oncology
- Biochemistry
Background:
- Ferroptosis is a regulated form of cell death with implications for cancer therapy.
- Understanding the molecular triggers of ferroptosis is crucial for developing novel anti-cancer strategies.
- 6-methoxyflavone is a natural compound with potential biological activities.
Purpose of the Study:
- To investigate the role of 6-methoxyflavone in inducing ferroptosis in HeLa cells.
- To elucidate the molecular mechanism underlying 6-methoxyflavone-induced ferroptosis.
Main Methods:
- Transmission electron microscopy (TEM) for cellular morphology.
- Assays for mitochondrial superoxide and glutathione levels.
- Multi-omics (proteomics, metabolomics), qPCR, and western blot for molecular profiling.
- Molecular docking and interaction analyses to identify binding targets.
Main Results:
- 6-methoxyflavone successfully induced ferroptosis in HeLa cells.
- Upregulation of SLC1A5 and mitochondrial superoxide was identified as a key mechanism.
- Molecular docking revealed a strong affinity between 6-methoxyflavone and SLC1A5, primarily via hydrophobic interactions.
Conclusions:
- 6-methoxyflavone induces ferroptosis in HeLa cells by altering ferroptosis-related gene, protein, and metabolite expression.
- SLC1A5 is identified as the core gene responsible for 6-methoxyflavone-induced ferroptosis and mitochondrial superoxide upregulation.
- These findings suggest 6-methoxyflavone's potential as an anti-cancer agent targeting ferroptosis.
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