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Verified CAS / Academic Author2 Decoded Studies

Prof. SHI Dan

Binzhou Medical University

Research Publications & English Decoded Briefs

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Acta Biochimica et Biophysica Sinica2025DOI: 10.3724/abbs.2025056

Triptonide facilitates autophagy-mediated apoptosis in esophageal squamous cell carcinoma by targeting the AMPK-mTOR-ULK1 axis

Triptonide (TN) is a small-molecule compound initially derived from Tripterygium wilfordii Hook. f used in traditional Chinese medicine. However, its potential antitumor mechanisms are still far from adequately understood. The purpose of this research is to elucidate the antitumor and pharmacological effects of TN on esophageal squamous cell carcinoma (ESCC). Functional assays, such as CCK-8 and colony formation assays, are used to evaluate the effects of TN on KYSE450 and KYSE510 cells. Subsequently, western blot analysis, Hoechst 33258 staining, flow cytometric analysis, autophagic flux detection, and transmission electron microscopy (TEM) are used to determine the effects of TN on apoptosis and autophagy in ESCC cells. Additionally, the autophagy inhibitor 3-methyladenine (3-MA) and the AMPK inhibitor dorsomorphin (Compound C, CC) are administered to explore the molecular mechanisms and crucial pathways in ESCC cells. Our findings provide strong evidence that TN induces autophagy-dependent apoptosis by targeting the AMPK-mTOR-ULK1 axis in ESCC cells. Collectively, this study sheds light on the anticancer mechanisms of TN in esophageal squamous cell carcinoma and suggests that TN is a promising candidate for the antitumor phytomedicine.

Acta Biochimica et Biophysica Sinica2025DOI: 10.3724/abbs.2025056

Triptonide facilitates autophagy-mediated apoptosis in esophageal squamous cell carcinoma by targeting the AMPK-mTOR-ULK1 axis

Esophageal squamous cell carcinoma (ESCC) accounts for 90% of global esophageal cancer cases, with high prevalence in Asia, East Africa, and South America. Current treatment relies on esophagectomy, which carries significant morbidity and limited efficacy, underscoring the urgent need for novel therapeutic agents. Triptonide (TN), a small-molecule compound derived from Tripterygium wilfordii Hook. f, exhibits potent antitumor activity, but its mechanisms in ESCC remain undefined. This study investigated TN-induced cytotoxicity in KYSE450 and KYSE510 ESCC cell lines using CCK-8 and colony formation assays. Western blot analysis, Hoechst 33258 staining, flow cytometry, autophagic flux detection, and transmission electron microscopy (TEM) assessed apoptosis and autophagy. Pharmacological inhibitors 3-methyladenine (3-MA) and dorsomorphin (Compound C, CC) were employed to dissect pathway involvement. Results demonstrate that TN induces autophagy-dependent apoptosis by targeting the AMPK-mTOR-ULK1 axis. TN treatment led to AMPK activation, mTOR inhibition, and ULK1 phosphorylation, triggering autophagic flux and subsequent apoptosis. Inhibition of autophagy with 3-MA or AMPK with CC attenuated TN-induced apoptosis, confirming the mechanistic dependency. These findings establish TN as a promising candidate for ESCC therapy and elucidate a novel molecular pathway for its anticancer effects.