Rotenone inhibited osteosarcoma metastasis by modulating ZO-2 expression and location via the ROS/Ca2+/AMPK pathway
Background Pulmonary metastases in osteosarcoma (OS) are associated with a poor prognosis. Rotenone has shown anti-cancer activity. However, its effects on metastasis and the underlying mechanisms remain unknown. This study investigated the potential use of Rotenone for OS treatment.Methods The effe...
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Taylor & Francis Group
2025-12-01
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| Series: | Redox Report |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/13510002.2025.2493556 |
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| author | Xiang Ma Zhen Li Hengwei Ma Kun Jiang Bao Chen Weiquan Wang Ziqiang Zhu Jianqiang Wang Zuozhang Yang Wang Yunqing Suwei Dong |
| author_facet | Xiang Ma Zhen Li Hengwei Ma Kun Jiang Bao Chen Weiquan Wang Ziqiang Zhu Jianqiang Wang Zuozhang Yang Wang Yunqing Suwei Dong |
| author_sort | Xiang Ma |
| collection | DOAJ |
| description | Background Pulmonary metastases in osteosarcoma (OS) are associated with a poor prognosis. Rotenone has shown anti-cancer activity. However, its effects on metastasis and the underlying mechanisms remain unknown. This study investigated the potential use of Rotenone for OS treatment.Methods The effect of Rotenone and ROS/Ca2+/AMPK/ZO-2 pathway on metastasis and EMT was evaluated by Western blot, Transwell and Wound healing. Flow cytometer was employed to measure the intracellular Ros and Ca2+ levels. The subcellular location of ZO-2 was detected by IF, interaction between AMPK and ZO-2 were examined by Co-IP. Then, subcutaneous tumor and metastasis models were used to evaluate the function of Rotenone in OS metastasis.Results Rotenone-induced ROS led to increased intracellular Ca2+, which promoted the EMT of OS cells through activation of AMPK and ZO-2 nuclear translocation. Inhibition of ROS production decreased intracellular Ca2+, restraining AMPK activity. Knock-down of ZO-2 significantly suppressed the anti-metastasis effects of Rotenone in OS cells. Moreover, Rotenone elevated p-AMPK and ZO-2 expression but inhibited EMT and lung metastasis in vivo.Conclusion These results provide evidence supporting an anti-metastatic effect of Rotenone. These findings support the use of Rotenone in the prevention of OS metastasis. |
| format | Article |
| id | doaj-art-d21e848664f943d591f13aa42cda2f56 |
| institution | DOAJ |
| issn | 1351-0002 1743-2928 |
| language | English |
| publishDate | 2025-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Redox Report |
| spelling | doaj-art-d21e848664f943d591f13aa42cda2f562025-08-20T03:18:12ZengTaylor & Francis GroupRedox Report1351-00021743-29282025-12-0130110.1080/13510002.2025.2493556Rotenone inhibited osteosarcoma metastasis by modulating ZO-2 expression and location via the ROS/Ca2+/AMPK pathwayXiang Ma0Zhen Li1Hengwei Ma2Kun Jiang3Bao Chen4Weiquan Wang5Ziqiang Zhu6Jianqiang Wang7Zuozhang Yang8Wang Yunqing9Suwei Dong10Department of Orthopaedics, The Third Affiliated Hospital of Kunming Medical University, Kunming, People’s Republic of ChinaDepartment of Medical Oncology, The Second Affiliated Hospital of Xuzhou Medical University, Xuzhou, People’s Republic of ChinaDepartment of Orthopaedics, The Second Affiliated Hospital of Xuzhou Medical University, Xuzhou, People’s Republic of ChinaDepartment of Orthopaedics, The Second Affiliated Hospital of Xuzhou Medical University, Xuzhou, People’s Republic of ChinaDepartment of Orthopaedics, The Second Affiliated Hospital of Xuzhou Medical University, Xuzhou, People’s Republic of ChinaDepartment of Orthopaedics, The Third Affiliated Hospital of Kunming Medical University, Kunming, People’s Republic of ChinaDepartment of Orthopaedics, The Second Affiliated Hospital of Xuzhou Medical University, Xuzhou, People’s Republic of ChinaDepartment of Orthopaedics, The Second Affiliated Hospital of Xuzhou Medical University, Xuzhou, People’s Republic of ChinaDepartment of Orthopaedics, The Third Affiliated Hospital of Kunming Medical University, Kunming, People’s Republic of ChinaDepartment of Orthopaedics, The Second Affiliated Hospital of Xuzhou Medical University, Xuzhou, People’s Republic of ChinaDepartment of Orthopaedics, The Second Affiliated Hospital of Xuzhou Medical University, Xuzhou, People’s Republic of ChinaBackground Pulmonary metastases in osteosarcoma (OS) are associated with a poor prognosis. Rotenone has shown anti-cancer activity. However, its effects on metastasis and the underlying mechanisms remain unknown. This study investigated the potential use of Rotenone for OS treatment.Methods The effect of Rotenone and ROS/Ca2+/AMPK/ZO-2 pathway on metastasis and EMT was evaluated by Western blot, Transwell and Wound healing. Flow cytometer was employed to measure the intracellular Ros and Ca2+ levels. The subcellular location of ZO-2 was detected by IF, interaction between AMPK and ZO-2 were examined by Co-IP. Then, subcutaneous tumor and metastasis models were used to evaluate the function of Rotenone in OS metastasis.Results Rotenone-induced ROS led to increased intracellular Ca2+, which promoted the EMT of OS cells through activation of AMPK and ZO-2 nuclear translocation. Inhibition of ROS production decreased intracellular Ca2+, restraining AMPK activity. Knock-down of ZO-2 significantly suppressed the anti-metastasis effects of Rotenone in OS cells. Moreover, Rotenone elevated p-AMPK and ZO-2 expression but inhibited EMT and lung metastasis in vivo.Conclusion These results provide evidence supporting an anti-metastatic effect of Rotenone. These findings support the use of Rotenone in the prevention of OS metastasis.https://www.tandfonline.com/doi/10.1080/13510002.2025.2493556RotenoneAMPKZO-2ROSCa2+metastasis |
| spellingShingle | Xiang Ma Zhen Li Hengwei Ma Kun Jiang Bao Chen Weiquan Wang Ziqiang Zhu Jianqiang Wang Zuozhang Yang Wang Yunqing Suwei Dong Rotenone inhibited osteosarcoma metastasis by modulating ZO-2 expression and location via the ROS/Ca2+/AMPK pathway Redox Report Rotenone AMPK ZO-2 ROS Ca2+ metastasis |
| title | Rotenone inhibited osteosarcoma metastasis by modulating ZO-2 expression and location via the ROS/Ca2+/AMPK pathway |
| title_full | Rotenone inhibited osteosarcoma metastasis by modulating ZO-2 expression and location via the ROS/Ca2+/AMPK pathway |
| title_fullStr | Rotenone inhibited osteosarcoma metastasis by modulating ZO-2 expression and location via the ROS/Ca2+/AMPK pathway |
| title_full_unstemmed | Rotenone inhibited osteosarcoma metastasis by modulating ZO-2 expression and location via the ROS/Ca2+/AMPK pathway |
| title_short | Rotenone inhibited osteosarcoma metastasis by modulating ZO-2 expression and location via the ROS/Ca2+/AMPK pathway |
| title_sort | rotenone inhibited osteosarcoma metastasis by modulating zo 2 expression and location via the ros ca2 ampk pathway |
| topic | Rotenone AMPK ZO-2 ROS Ca2+ metastasis |
| url | https://www.tandfonline.com/doi/10.1080/13510002.2025.2493556 |
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