Targeting Galectin-1 with Triptolide Induces Ferroptosis in Oral Squamous Cell Carcinoma

Area of Science:

• Oncology
• Cell Biology
• Biochemistry

Background:

• Oral squamous cell carcinoma (OSCC) presents significant treatment challenges, especially in advanced stages, due to therapy resistance.
• Ferroptosis, a cell death pathway triggered by lipid peroxidation, offers a potential therapeutic vulnerability in cancer.
• Galectin-1 (Gal-1/LGALS1), often overexpressed in OSCC, is linked to tumor progression and poor prognosis, but its role in ferroptosis is unclear.

Purpose of the Study:

• To investigate if Triptolide (TPL) affects ferroptosis in OSCC by modulating Galectin-1 (Gal-1) expression.
• To assess the impact of TPL on OSCC cell viability, lipid reactive oxygen species (ROS), and glutathione peroxidase 4 (GPX4) levels.
• To analyze the correlation between Gal-1 expression, patient survival, and TPL's in vivo antitumor effects.

Main Methods:

• OSCC cell lines (SAS, HSC-3) were treated with TPL to measure cell viability, lipid ROS, and GPX4 expression.
• The Cancer Genome Atlas (TCGA) database was analyzed for Gal-1 expression patterns and survival associations in OSCC.
• An OSCC xenograft mouse model was employed to evaluate TPL's antitumor efficacy and ferroptosis marker changes.

Main Results:

• TPL treatment decreased OSCC cell viability and increased lipid ROS, while downregulating GPX4 expression.
• TPL exposure led to reduced Gal-1 expression both in vitro and in vivo.
• Elevated Gal-1 expression in TCGA data was significantly associated with poorer overall survival in OSCC patients.

Conclusions:

• TPL induces ferroptosis-related responses in OSCC, partly through the downregulation of Gal-1.
• Gal-1 may influence ferroptosis susceptibility in OSCC, representing a potential therapeutic target.
• Targeting the Gal-1 pathway warrants further investigation for novel OSCC treatment strategies.