2. Academic Validation
  3. Formosanin C induces autophagy-mediated cell death in hepatocellular carcinoma through activating DUSP1/AMPK/ULK1/Beclin1 signaling pathway

Formosanin C induces autophagy-mediated cell death in hepatocellular carcinoma through activating DUSP1/AMPK/ULK1/Beclin1 signaling pathway

  • Phytomedicine. 2025 Mar:138:156404. doi: 10.1016/j.phymed.2025.156404.
Zhikai Wen 1,  Jinxia Qi 2,  Qingqing Ruan 3,  Chunmei Wen 3,  Gang Huang 4,  Zhan Yang 5,  Jiale Xu 3,  Zongjing Chen 6,  Jie Deng 7
Affiliations

Affiliations

  • 1 Zhejiang Key Laboratory of Intelligent Cancer Biomarker Discovery and Translation, First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325035, China; Department of Hepatopancreatobiliary Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
  • 2 Biobank, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang, PR China.
  • 3 Zhejiang Key Laboratory of Intelligent Cancer Biomarker Discovery and Translation, First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325035, China.
  • 4 Zhejiang Key Laboratory of Intelligent Cancer Biomarker Discovery and Translation, First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325035, China; Department of thoracic surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
  • 5 School of Stomatology, Wenzhou Medical University, Wenzhou 325000, China.
  • 6 Department of Hepatopancreatobiliary Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China. Electronic address: czjasq@sina.com.
  • 7 Zhejiang Key Laboratory of Intelligent Cancer Biomarker Discovery and Translation, First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325035, China. Electronic address: dengjiewz@163.com.
PMID: 39862789 DOI: 10.1016/j.phymed.2025.156404
Abstract

Background: Hepatocellular carcinoma (HCC) accounts for the majority of primary liver cancers and is associated with poor survival. Formosanin C (FC) is a diosgenin glycoside extracted from Paris polyphylla. Therapeutic effects of FC against HCC malignancies remain unclear.

Purpose: This study aimed to understand the anti-HCC effects of FC and to disclose the underlying mechanisms.

Study design: We evaluated the effects of FC on HCC malignancies by using two HCC cell lines, HepG2 and Huh-7, and a xenograft model.

Methods: Multiple assessment methods were used, including CCK-8, colony formation, flow cytometry, wound healing, transwell and Western blot. Bioinformatic analyses such as network pharmacology were also employed. Xenograft mouse model was used to evaluate in vivo efficacy.

Results: FC treatment remarkedly suppressed HepG2 and Huh-7 cell proliferation, migration and invasion, and induced cell Apoptosis. Such anti-HCC effects of FC mainly attributed to the upregulation of DUSP1 expression and the subsequent activation of Autophagy via AMPK/ULK1/Beclin1 axis. Inhibition of Autophagy weakened the therapeutic effects of FC. Xenograft model analysis provided in vivo evidence that FC suppressed HCC tumor growth via DUSP1.

Conclusions: FC is therapeutically effective to suppress HCC malignancies principally via activation of the DUSP1/AMPK/ULK1/Beclin1-mediated Autophagy. Our findings provide a novel promising drug candidate for treating HCC.

Keywords

Autophagy; DUSP1; Formosanin C; hepatocellular carcinoma.

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