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

Authors

Wei-Tso Chia, Cheng-Yu Yang, Wei-Chin Chang, Chang-Huei Tsao, Chih-Kung Lin, Sien-Lin Ho, Chin-Shan Kuo, Chi-Tsung Wu, Ching-Hsien Tsai, Yu-Hsuan Li, Kuei-Yuan Chen, Gu-Jiun Lin, Chun-Shu Lin, Cheng-Chih Hsieh, Yuan-Wu Chen

Published in

Cancers. Volume 18. Issue 5. Feb 28, 2026. Epub Feb 28, 2026.

Abstract

Background: Oral squamous cell carcinoma (OSCC) remains clinically challenging, particularly in advanced disease, where treatment resistance limits therapeutic outcomes. Ferroptosis, an iron-dependent form of regulated cell death driven by lipid peroxidation, has emerged as a potential anticancer vulnerability. Galectin-1 (Gal-1/LGALS1), a β-galactoside-binding lectin frequently overexpressed in OSCC, is associated with tumor progression and unfavorable prognosis; however, its involvement in ferroptosis regulation remains incompletely understood. Methods: To investigate whether Triptolide (TPL) influences ferroptosis-associated responses through Gal-1 modulation, OSCC cell lines (SAS and HSC-3) were treated with TPL and analyzed for cell viability, lipid reactive oxygen species (ROS) accumulation, and glutathione peroxidase 4 (GPX4) expression. Publicly available The Cancer Genome Atlas (TCGA) datasets were examined to evaluate Gal-1 expression patterns and survival associations. An OSCC xenograft mouse model was further used to assess the antitumor effects of TPL and changes in ferroptosis-related markers in vivo. Results: TPL treatment reduced cell viability and increased lipid ROS accumulation in OSCC cells, accompanied by downregulation of GPX4 expression. Gal-1 expression was also decreased following TPL exposure in vitro and in xenograft tumors. Analysis of TCGA data revealed that elevated Gal-1 expression was significantly associated with poorer overall survival in OSCC patients. Conclusions: These findings indicate that TPL induces ferroptosis-associated responses in OSCC and suggest that this effect is partly mediated through modulation of Gal-1 expression. Gal-1 may represent a clinically relevant factor influencing ferroptosis susceptibility, and targeting this pathway warrants further investigation as a potential therapeutic strategy for OSCC.

PMID:
41827716
Bibliographic data and abstract were imported from PubMed on 14 Sep 2026.

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