Ovatodiolide triggers ferroptosis in high-grade serous ovarian cancer through HMOX1 upregulation
High-grade serous ovarian carcinoma (HGSC) is the most aggressive and lethal gynecological malignancy, largely due to its asymptomatic early stages and late-stage diagnosis. Current standard treatments involve surgical resection combined with platinum-based chemotherapy, yet recurrence rates remain...
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Elsevier
2025-09-01
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| Series: | Molecular Therapy: Oncology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S295032992500092X |
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| author | Yew-Min Tzeng Aye Aye Khine Hsuan-Shun Huang Tang-Yuan Chu |
| author_facet | Yew-Min Tzeng Aye Aye Khine Hsuan-Shun Huang Tang-Yuan Chu |
| author_sort | Yew-Min Tzeng |
| collection | DOAJ |
| description | High-grade serous ovarian carcinoma (HGSC) is the most aggressive and lethal gynecological malignancy, largely due to its asymptomatic early stages and late-stage diagnosis. Current standard treatments involve surgical resection combined with platinum-based chemotherapy, yet recurrence rates remain high, highlighting the urgent need for more effective therapeutic options. Ovatodiolide, a bioactive macrocyclic diterpenoid derived from traditional medicinal herbs, has been reported to possess anti-cancer properties against various malignancies. In this study, we demonstrated that ovatodiolide exerts potent cytotoxic effects on both HGSC cells and their precursor cells. RNA sequencing (RNA-seq) analysis reveals that the cytotoxicity of ovatodiolide is associated with the upregulation of heme oxygenase 1 (HMOX-1), along with the activation of oxidative stress and ferroptosis, suggesting a distinct cell death mechanism. These findings demonstrate that ovatodiolide induces HGSC cell death through a unique mode of action and highlight its potential as a promising therapeutic agent to complement or enhance existing treatment strategies. |
| format | Article |
| id | doaj-art-f32afbf467c247ec9581bd669cee07bb |
| institution | DOAJ |
| issn | 2950-3299 |
| language | English |
| publishDate | 2025-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Oncology |
| spelling | doaj-art-f32afbf467c247ec9581bd669cee07bb2025-08-20T02:46:25ZengElsevierMolecular Therapy: Oncology2950-32992025-09-0133320102310.1016/j.omton.2025.201023Ovatodiolide triggers ferroptosis in high-grade serous ovarian cancer through HMOX1 upregulationYew-Min Tzeng0Aye Aye Khine1Hsuan-Shun Huang2Tang-Yuan Chu3Department of Applied Science, National Taitung University, Sec. 2, University Road, Taitung 95092, Taiwan, ROC; Department of Applied Chemistry, Chaoyang University of Technology, Taichung 41349, Taiwan, ROCCenter for Prevention and Therapy of Gynecological Cancers, Department of Research, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien 970, Taiwan, ROCCenter for Prevention and Therapy of Gynecological Cancers, Department of Research, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien 970, Taiwan, ROC; Corresponding author: Hsuan-Shun Huang, Center for Prevention and Therapy of Gynecological Cancers, Department of Research, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien 970, Taiwan, ROCCenter for Prevention and Therapy of Gynecological Cancers, Department of Research, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien 970, Taiwan, ROC; Department of Obstetrics & Gynecology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien 970, Taiwan, ROC; Institute of Medical Sciences, Tzu Chi University, Hualien 970, Taiwan, ROC; Corresponding author: Tang-Yuan Chu, Institute of Medical Sciences, Tzu Chi University, Hualien 970, Taiwan, ROCHigh-grade serous ovarian carcinoma (HGSC) is the most aggressive and lethal gynecological malignancy, largely due to its asymptomatic early stages and late-stage diagnosis. Current standard treatments involve surgical resection combined with platinum-based chemotherapy, yet recurrence rates remain high, highlighting the urgent need for more effective therapeutic options. Ovatodiolide, a bioactive macrocyclic diterpenoid derived from traditional medicinal herbs, has been reported to possess anti-cancer properties against various malignancies. In this study, we demonstrated that ovatodiolide exerts potent cytotoxic effects on both HGSC cells and their precursor cells. RNA sequencing (RNA-seq) analysis reveals that the cytotoxicity of ovatodiolide is associated with the upregulation of heme oxygenase 1 (HMOX-1), along with the activation of oxidative stress and ferroptosis, suggesting a distinct cell death mechanism. These findings demonstrate that ovatodiolide induces HGSC cell death through a unique mode of action and highlight its potential as a promising therapeutic agent to complement or enhance existing treatment strategies.http://www.sciencedirect.com/science/article/pii/S295032992500092Xhigh-grade serous ovarian carcinomaovatodiolideheme oxygenase 1ferroptosis |
| spellingShingle | Yew-Min Tzeng Aye Aye Khine Hsuan-Shun Huang Tang-Yuan Chu Ovatodiolide triggers ferroptosis in high-grade serous ovarian cancer through HMOX1 upregulation Molecular Therapy: Oncology high-grade serous ovarian carcinoma ovatodiolide heme oxygenase 1 ferroptosis |
| title | Ovatodiolide triggers ferroptosis in high-grade serous ovarian cancer through HMOX1 upregulation |
| title_full | Ovatodiolide triggers ferroptosis in high-grade serous ovarian cancer through HMOX1 upregulation |
| title_fullStr | Ovatodiolide triggers ferroptosis in high-grade serous ovarian cancer through HMOX1 upregulation |
| title_full_unstemmed | Ovatodiolide triggers ferroptosis in high-grade serous ovarian cancer through HMOX1 upregulation |
| title_short | Ovatodiolide triggers ferroptosis in high-grade serous ovarian cancer through HMOX1 upregulation |
| title_sort | ovatodiolide triggers ferroptosis in high grade serous ovarian cancer through hmox1 upregulation |
| topic | high-grade serous ovarian carcinoma ovatodiolide heme oxygenase 1 ferroptosis |
| url | http://www.sciencedirect.com/science/article/pii/S295032992500092X |
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