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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MDPI AG
2025-02-01
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| Online Access: | https://www.mdpi.com/1420-3049/30/5/1095 |
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| author | Ruyu Cao Yuhui Liu Jiahe Bao Mingming Rong Jing Xu Haibing Liao Yuanqiang Guo |
| author_facet | Ruyu Cao Yuhui Liu Jiahe Bao Mingming Rong Jing Xu Haibing Liao Yuanqiang Guo |
| author_sort | Ruyu Cao |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-70f6882a63bd487d813adf558fa48fe7 |
| institution | DOAJ |
| issn | 1420-3049 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | MDPI AG |
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| series | Molecules |
| spelling | doaj-art-70f6882a63bd487d813adf558fa48fe72025-08-20T02:59:00ZengMDPI AGMolecules1420-30492025-02-01305109510.3390/molecules30051095Faberidilactone A, a Sesquiterpene Dimer, Inhibits Hepatocellular Carcinoma Progression Through Apoptosis, Ferroptosis, and Anti-Metastatic MechanismsRuyu Cao0Yuhui Liu1Jiahe Bao2Mingming Rong3Jing Xu4Haibing Liao5Yuanqiang Guo6State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy, and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300350, ChinaState Key Laboratory of Medicinal Chemical Biology, College of Pharmacy, and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300350, ChinaState Key Laboratory of Medicinal Chemical Biology, College of Pharmacy, and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300350, ChinaState Key Laboratory of Medicinal Chemical Biology, College of Pharmacy, and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300350, ChinaState Key Laboratory of Medicinal Chemical Biology, College of Pharmacy, and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300350, ChinaState Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources, Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources (Ministry of Education of China), Collaborative Innovation Center for Guangxi Ethnic Medicine, School of Chemistry and Pharmaceutical Sciences, Guangxi Normal University, Guilin 541004, ChinaState Key Laboratory of Medicinal Chemical Biology, College of Pharmacy, and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300350, ChinaCancer 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.https://www.mdpi.com/1420-3049/30/5/1095faberidilactone Asesquiterpenoid dimerSTAT3FAKzebrafishantitumor |
| spellingShingle | Ruyu Cao Yuhui Liu Jiahe Bao Mingming Rong Jing Xu Haibing Liao Yuanqiang Guo Faberidilactone A, a Sesquiterpene Dimer, Inhibits Hepatocellular Carcinoma Progression Through Apoptosis, Ferroptosis, and Anti-Metastatic Mechanisms Molecules faberidilactone A sesquiterpenoid dimer STAT3 FAK zebrafish antitumor |
| title | Faberidilactone A, a Sesquiterpene Dimer, Inhibits Hepatocellular Carcinoma Progression Through Apoptosis, Ferroptosis, and Anti-Metastatic Mechanisms |
| title_full | Faberidilactone A, a Sesquiterpene Dimer, Inhibits Hepatocellular Carcinoma Progression Through Apoptosis, Ferroptosis, and Anti-Metastatic Mechanisms |
| title_fullStr | Faberidilactone A, a Sesquiterpene Dimer, Inhibits Hepatocellular Carcinoma Progression Through Apoptosis, Ferroptosis, and Anti-Metastatic Mechanisms |
| title_full_unstemmed | Faberidilactone A, a Sesquiterpene Dimer, Inhibits Hepatocellular Carcinoma Progression Through Apoptosis, Ferroptosis, and Anti-Metastatic Mechanisms |
| title_short | Faberidilactone A, a Sesquiterpene Dimer, Inhibits Hepatocellular Carcinoma Progression Through Apoptosis, Ferroptosis, and Anti-Metastatic Mechanisms |
| title_sort | faberidilactone a a sesquiterpene dimer inhibits hepatocellular carcinoma progression through apoptosis ferroptosis and anti metastatic mechanisms |
| topic | faberidilactone A sesquiterpenoid dimer STAT3 FAK zebrafish antitumor |
| url | https://www.mdpi.com/1420-3049/30/5/1095 |
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