PUBLICATION
8-epi-Helenalin Suppresses Tumorigenesis and Metastasis by Modulating the STAT3/FAK Signaling Axis
- Authors
- Nie, F., Jiang, H., Cao, R., Rong, M., Bao, J., Wang, C., Xu, J., Guo, Y.
- ID
- ZDB-PUB-250831-4
- Date
- 2025
- Source
- European Journal of Pharmacology : 178111178111 (Journal)
- Registered Authors
- Keywords
- Angiogenesis, Apoptosis, Sesquiterpene, Zebrafish, ferroptosis
- MeSH Terms
-
- Animals
- Antineoplastic Agents, Phytogenic*/pharmacology
- Apoptosis/drug effects
- Carcinogenesis*/drug effects
- Carcinogenesis*/pathology
- Carcinoma, Hepatocellular*/drug therapy
- Carcinoma, Hepatocellular*/metabolism
- Carcinoma, Hepatocellular*/pathology
- Cell Movement/drug effects
- Cell Proliferation/drug effects
- Ferroptosis/drug effects
- Focal Adhesion Kinase 1*/metabolism
- Hep G2 Cells
- Humans
- Liver Neoplasms*/drug therapy
- Liver Neoplasms*/metabolism
- Liver Neoplasms*/pathology
- Neoplasm Metastasis
- Reactive Oxygen Species/metabolism
- STAT3 Transcription Factor*/metabolism
- Sesquiterpenes*/pharmacology
- Sesquiterpenes*/therapeutic use
- Sesquiterpenes, Guaiane
- Signal Transduction*/drug effects
- Xenograft Model Antitumor Assays
- Zebrafish
- PubMed
- 40885232 Full text @ Eur. J. Pharmacol.
Citation
Nie, F., Jiang, H., Cao, R., Rong, M., Bao, J., Wang, C., Xu, J., Guo, Y. (2025) 8-epi-Helenalin Suppresses Tumorigenesis and Metastasis by Modulating the STAT3/FAK Signaling Axis. European Journal of Pharmacology. :178111178111.
Abstract
Hepatocellular carcinoma (HCC) poses a significant global health challenge, highlighting the importance of discovering novel anticancer lead compounds from natural products. In this study, we isolated the sesquiterpene lactone 8-epi-helenalin from the dried flowers of Inula japonica. In vitro experiments demonstrated its potent antiproliferative activity against various tumor cell lines, including human HCC cells (HepG2). Using a zebrafish xenograft model, we further confirmed its in vivo efficacy in suppressing tumor growth and metastasis. Given its remarkable antitumor effects, we investigated the underlying mechanisms. Our findings reveal that 8-epi-helenalin exerts multitargeted anticancer activity through: inducing apoptosis via Signal transducer and activator of transcription 3 (STAT3) signaling pathway modulation, inhibiting tumor cell migration by suppressing Focal Adhesion Kinase (FAK) signaling, triggering ferroptosis through increased lipid ROS accumulation and reduced glutathione (GSH) levels, and suppressing tumor angiogenesis. In conclusion, 8-epi-helenalin inhibits HCC progression through multiple pathways and targets, demonstrating promising potential as a therapeutic candidate for HCC treatment.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping