To investigate whether loratadine induces ferroptosis and overcomes chemoresistance in MDR1-overexpressing KB-V-1 cells, addressing a critical barrier in cancer therapy.
Cell death was rescued by ferroptosis inhibitors, confirming ferroptosis as the primary mechanism, which is crucial for understanding treatment strategies.
Loratadine suppressed cystine uptake, depleted glutathione, elevated labile iron, and promoted lipid peroxidation, aligning with the expected hallmarks of ferroptosis.
RNA-seq identified 1,861 differentially expressed genes, with upregulation of stress response genes confirmed, emphasizing the molecular changes induced by loratadine.
Loratadine reduced MDR1/P-glycoprotein expression and suppressed tumor growth in vivo, suggesting its potential as a therapeutic agent.
Interpretation:
Loratadine induces ferroptosis in MDR1-overexpressing cells through multiple mechanisms, including cystine uptake inhibition and glutathione depletion, while also downregulating MDR1/P-glycoprotein.
Limitations:
The study is preclinical and requires further validation in clinical settings to establish efficacy and safety.
The long-term effects and safety of loratadine in cancer therapy are not fully established, necessitating comprehensive studies.
Conclusion:
These findings support loratadine as a candidate for repurposing in ferroptosis-based cancer therapy targeting multidrug resistance, with implications for improving treatment outcomes.
