Xanthohumol Regulates Mitophagy in Osteosarcoma Cells via AMPK‐ULK1‐FUNDC1 Signaling Pathway
Fuente:
Wiley Open Access
Enregistré dans:
| Auteurs principaux: | , , , , , , , |
|---|---|
| Format: | Artículo Open Access |
| Publié: |
Wiley
2025
|
| Sujets: | |
| Accès en ligne: | |
| Tags: |
Ajouter un tag
Pas de tags, Soyez le premier à ajouter un tag!
|
| _version_ | 1867002391186898944 |
|---|---|
| author | Qiaofeng Ge Zhiliang Yan Qian Tian Jiyan Zhang Jia Li Fang Cai Long Zhang Yonggang Zhu |
| author_facet | Qiaofeng Ge Zhiliang Yan Qian Tian Jiyan Zhang Jia Li Fang Cai Long Zhang Yonggang Zhu Qiaofeng Ge Zhiliang Yan Qian Tian Jiyan Zhang Jia Li Fang Cai Long Zhang Yonggang Zhu |
| collection | Wiley Open Access |
| contents | Xanthohumol Regulates Mitophagy in Osteosarcoma Cells via AMPK‐ULK1‐FUNDC1 Signaling Pathway Qiaofeng Ge Zhiliang Yan Qian Tian Jiyan Zhang Jia Li Fang Cai Long Zhang Yonggang Zhu Phytotherapy Research ABSTRACTOsteosarcoma (OS) is the most common primary bone malignancy. The therapeutic efficacy for OS patients has remained stagnant in recent decades. Xanthohumol (XN), a flavonoid naturally found in hops, has demonstrated significant anticancer properties in lung and breast cancer. However, its effect on OS and the underlying molecular mechanisms remains uncertain. Therefore, the purpose of this study is to explore the relationship between XN and OS. Firstly, we assessed the impact of XN on OS cell proliferation and migration using CCK‐8, wound‐healing, transwell, and clonogenicity assays. Subsequently, we examined the effect of XN on mitophagy in OS cells through flow cytometry, immunofluorescence, transmission electron microscopy, and western blot analysis. Finally, we constructed siRNA targeting AMPK to validate the pathway. In vitro, we demonstrated that XN inhibited the proliferation and migration of OS cells in a concentration‐ and time‐dependent manner. Furthermore, XN induced mitochondrial damage in OS cells and increased reactive oxygen species (ROS) levels. RNA‐seq analysis suggested a potential mitophagy pathway, which we confirmed experimentally by showing that XN reduced ATP levels, altered mitochondrial membrane potential, and increased the expression of Atg5, Beclin‐1, and LC3 proteins. Interestingly, the mitophagy inhibitor Mdivi‐1 reversed the damage caused by XN to OS cells. Furthermore, we found that XN induced mitophagy and exerted anti‐OS effects through the activation of the AMPK‐ULK1‐FUNDC1 signaling pathway, which was effectively reversed after AMPK knockdown. In vivo, we demonstrated the therapeutic potential of XN using a subcutaneous OS nude mouse model without any organ toxicity. XN emerges as a promising pharmaceutical agent for targeting OS. 10.1002/ptr.8468 http://onlinelibrary.wiley.com/termsAndConditions#vor |
| doi_str_mv | 10.1002/ptr.8468 |
| format | Artículo Open Access |
| id | wiley_oa_10_1002_ptr_8468 |
| institution | Wiley Open Access |
| license_str_mv | http://onlinelibrary.wiley.com/termsAndConditions#vor |
| publishDate | 2025 |
| publisher | Wiley |
| record_format | wiley_oa |
| spellingShingle | Xanthohumol Regulates Mitophagy in Osteosarcoma Cells via AMPK‐ULK1‐FUNDC1 Signaling Pathway Qiaofeng Ge Zhiliang Yan Qian Tian Jiyan Zhang Jia Li Fang Cai Long Zhang Yonggang Zhu Phytotherapy Research Xanthohumol Regulates Mitophagy in Osteosarcoma Cells via AMPK‐ULK1‐FUNDC1 Signaling Pathway Qiaofeng Ge Zhiliang Yan Qian Tian Jiyan Zhang Jia Li Fang Cai Long Zhang Yonggang Zhu Phytotherapy Research ABSTRACTOsteosarcoma (OS) is the most common primary bone malignancy. The therapeutic efficacy for OS patients has remained stagnant in recent decades. Xanthohumol (XN), a flavonoid naturally found in hops, has demonstrated significant anticancer properties in lung and breast cancer. However, its effect on OS and the underlying molecular mechanisms remains uncertain. Therefore, the purpose of this study is to explore the relationship between XN and OS. Firstly, we assessed the impact of XN on OS cell proliferation and migration using CCK‐8, wound‐healing, transwell, and clonogenicity assays. Subsequently, we examined the effect of XN on mitophagy in OS cells through flow cytometry, immunofluorescence, transmission electron microscopy, and western blot analysis. Finally, we constructed siRNA targeting AMPK to validate the pathway. In vitro, we demonstrated that XN inhibited the proliferation and migration of OS cells in a concentration‐ and time‐dependent manner. Furthermore, XN induced mitochondrial damage in OS cells and increased reactive oxygen species (ROS) levels. RNA‐seq analysis suggested a potential mitophagy pathway, which we confirmed experimentally by showing that XN reduced ATP levels, altered mitochondrial membrane potential, and increased the expression of Atg5, Beclin‐1, and LC3 proteins. Interestingly, the mitophagy inhibitor Mdivi‐1 reversed the damage caused by XN to OS cells. Furthermore, we found that XN induced mitophagy and exerted anti‐OS effects through the activation of the AMPK‐ULK1‐FUNDC1 signaling pathway, which was effectively reversed after AMPK knockdown. In vivo, we demonstrated the therapeutic potential of XN using a subcutaneous OS nude mouse model without any organ toxicity. XN emerges as a promising pharmaceutical agent for targeting OS. 10.1002/ptr.8468 http://onlinelibrary.wiley.com/termsAndConditions#vor |
| title | Xanthohumol Regulates Mitophagy in Osteosarcoma Cells via AMPK‐ULK1‐FUNDC1 Signaling Pathway |
| topic | Phytotherapy Research |
| url | https://onlinelibrary.wiley.com/doi/10.1002/ptr.8468 |