Authors
Yihong Shen, Leping He, Chenglong Zheng, Dongmeng Liu, Zongmao He, Yuxia Zou, Guo-Sheng Wu, Chengwei He, Xiaofeng Wang, Ren-Bo Ding, Jiaolin Bao
Published in
Toxicology and applied pharmacology. Pages 118021. Aug 29, 2026. Epub Aug 29, 2026.
Abstract
Sertraline, a widely used antidepressant, has shown emerging anticancer activity, but its metabolic mechanism in colorectal cancer (CRC) remains unclear. In this study, we evaluated the in vivo antitumor effect of sertraline using a CT26 tumor-bearing BALB/c mouse model, and performed UPLC-MS-based untargeted metabolomics to characterize serum metabolic alterations. Our results found that sertraline significantly inhibited tumor growth in BALB/c mice and partially reversed tumor-associated metabolic disturbances. Notably, levels of arachidonic acid (AA), 11,12-epoxyeicosatrienoic acid (11,12-EET), and 12-KETE were markedly elevated in the tumor model group but shifted toward normal levels after sertraline treatment. Pathway analysis identified arachidonic acid metabolism as the most significantly affected pathway, and Western blot confirmed that sertraline downregulated ALOXE3 expression in both tumor tissues and CT26 cells. ROC analysis revealed that a panel of only two metabolites achieved an AUC of 0.845, demonstrating good discriminatory ability between the tumor model and sertraline-treated groups, while expanding to ten metabolites further improved the AUC to 0.975 (95% CI: 0.800-1.000). These findings suggest that sertraline exerts antitumor effects in CRC associated with metabolic remodeling of arachidonic acid metabolism and altered ALOXE3 expression, providing preclinical evidence supporting further investigation of sertraline as a potential drug-repurposing candidate for CRC.
PMID:
42668098
Bibliographic data and abstract were imported from PubMed on 30 Aug 2026.
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