Clinical Report: Utilizing loratadine to promote ferroptosis and address multidrug resistance
Overview
Loratadine, an FDA-approved antihistamine, has been shown to induce ferroptosis in multidrug-resistant KB-V-1 cells, overcoming resistance mechanisms. This study highlights loratadine's potential as a repurposed agent to enhance chemotherapy efficacy without systemic toxicity.
Background
Multidrug resistance (MDR) significantly limits the effectiveness of chemotherapy in cancer treatment, often leading to treatment failure. Ferroptosis, a regulated form of cell death characterized by lipid peroxidation, presents a novel approach to target MDR cells. Understanding how to induce ferroptosis could provide new therapeutic strategies for overcoming resistance in various cancers.
Data Highlights
Cell Line
IC50 (µM)
KB-V-1
2.0
KB-3–1
48.45
Key Findings
Loratadine selectively inhibited the viability of KB-V-1 cells while sparing KB-3–1 cells.
Cell death in KB-V-1 was confirmed as ferroptosis, as it was rescued by ferroptosis inhibitors.
Loratadine suppressed cystine uptake and depleted glutathione, leading to increased lipid peroxidation.
RNA sequencing revealed 1,861 differentially expressed genes, with significant upregulation of stress response genes.
Loratadine reduced the expression of MDR1/P-glycoprotein, a key player in multidrug resistance.
In vivo studies demonstrated that loratadine suppressed tumor growth and enhanced the efficacy of paclitaxel without systemic toxicity.
Clinical Implications
The findings suggest that loratadine could be a viable option for enhancing the effectiveness of chemotherapy in patients with multidrug-resistant cancers. Clinicians may consider repurposing loratadine to exploit its ferroptosis-inducing properties as part of a combination therapy strategy.
Conclusion
Loratadine shows promise as a repurposed agent to induce ferroptosis in multidrug-resistant cancer cells, potentially improving treatment outcomes. Further clinical investigations are warranted to validate these preclinical findings.
