5-Aminolevulinic Acid-Based Photodynamic Therapy Treatment Attenuate E6E7 Oncoprotein-Induced Ferroptosis in HaCaT Cells

Significance This study demonstrates the potential of 5-aminolevulinic acid-based photodynamic therapy (ALA-PDT) to attenuate E6E7 oncoprotein-induced ferroptosis in HaCaT cells, providing insights into novel therapeutic strategies for HPV-related skin diseases. Approach HaCaT cells were transfected with HPV E6E7 oncoproteins to establish a ferroptosis model. Cells were pretreated with 5-ALA and subjected to PDT with light activation. Ferroptosis was assessed by measuring cell viability, malondialdehyde, iron levels, lipid peroxidation (C11-BODIPY), and total glutathione. Western blot analysis was performed to evaluate the effects of PDT on ferroptosis-related signaling pathways. Results ALA-PDT treatment improved cell viability, reduced MDA, and iron levels, and decreased lipid peroxidation in E6E7-transfected HaCaT cells. Furthermore, PDT restored total GSH levels and inhibited ferroptosis-related signaling pathways, including upregulation of GPX4 and downregulation of ACSL4. Conclusions ALA-PDT effectively attenuates E6E7 oncoprotein-induced ferroptosis in human epidermal keratinocytes, suggesting its potential as a therapeutic strategy for HPV-related skin diseases.