Faberidilactone A, a Sesquiterpene Dimer, Inhibits Hepatocellular Carcinoma Progression Through Apoptosis, Ferroptosis, and Anti-Metastatic Mechanisms
Cancer remains a significant global public health challenge, with hepatocellular carcinoma (HCC) ranking among the top five malignancies in terms of mortality. Faberidilactone A, a sesquiterpenoid dimer isolated from <i>Inula japonica</i>, exhibits potent cytotoxicity against various hum...
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| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-02-01
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| Series: | Molecules |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1420-3049/30/5/1095 |
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| Summary: | Cancer remains a significant global public health challenge, with hepatocellular carcinoma (HCC) ranking among the top five malignancies in terms of mortality. Faberidilactone A, a sesquiterpenoid dimer isolated from <i>Inula japonica</i>, exhibits potent cytotoxicity against various human tumor cell lines and demonstrates remarkable antitumor potential. In vitro studies using HepG2 cells revealed that faberidilactone A induces apoptosis and ferroptosis, causes cell cycle arrest, enhances the production of intracellular reactive oxygen species (ROS), and disrupts mitochondrial function. Mechanistic investigations via Western blot analysis indicated that faberidilactone A impedes HepG2 cell proliferation by modulating the signal transducer and activator of the transcription 3 (STAT3) signaling pathway and inhibits metastasis by affecting the focal adhesion kinase (FAK) pathway. In vivo experiments using a zebrafish model demonstrated that faberidilactone A effectively suppresses the dissemination and metastasis of HepG2 cells and exhibits anti-angiogenic properties. When the concentration of faberidilactone A reached 10 µM, the inhibition rates of tumor proliferation, migration, and intersegmental vessels (ISVs) length were 76.9%, 72.6%, and 46.2%, respectively. These findings underscore the therapeutic potential of faberidilactone A as a promising agent for HCC treatment. |
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| ISSN: | 1420-3049 |