Ferroptosis Induction Enhances Photodynamic Therapy Efficacy for OLK

Area of Science:

• Oncology
• Biochemistry
• Photomedicine

Background:

• Oral leukoplakia (OLK) is a significant oral potentially malignant disorder with unpredictable malignant transformation.
• Photodynamic therapy (PDT) shows promise for OLK treatment, but its efficacy is variable.
• Ferroptosis, a regulated cell death pathway, is implicated in cancer and may offer synergistic effects with antitumor therapies.

Purpose of the Study:

• To investigate whether inducing ferroptosis can improve the efficacy of 5-aminolevulinic acid photodynamic therapy (ALA-PDT) in treating OLK.

Main Methods:

• Analyzed solute carrier family 7 member 11 (SLC7A11) expression in OLK patients unresponsive to ALA-PDT.
• Investigated ferroptosis induction by erastin and its combined effect with ALA-PDT on OLK cells.
• Evaluated the combined modality in a 4-nitroquinoline-1-oxide (4NQO)-induced OLK mouse model.

Main Results:

• High SLC7A11 expression correlated with poor ALA-PDT response in OLK.
• ALA-PDT induced ferroptosis in OLK cells.
• Erastin-induced ferroptosis combined with ALA-PDT enhanced OLK cell death and reduced 4NQO-induced OLK lesions in mice.

Conclusions:

• Ferroptosis induction, particularly with erastin, can synergistically enhance ALA-PDT efficacy for OLK.
• This combined approach disrupts the antioxidant system and increases reactive oxygen species, leading to apoptosis.
• Ferroptosis induction represents a promising strategy to improve ALA-PDT outcomes in oral potentially malignant disorders.