Hyptolide induces ER stress-mediated cell death and enhances GSK3β-regulated cisplatin chemosensitivity in ovarian cancer
Abstract Background Ovarian cancer is a highly prevalent cancer among women with a high risk for relapse and drug resistance. Seventy eight percent of women diagnosed with ovarian cancer live for at least one year after diagnosis. Hyptolide, a natural compound, has been shown to act as an anti-infla...
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| Format: | Article |
| Language: | English |
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BMC
2025-06-01
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| Series: | Journal of Ovarian Research |
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| Online Access: | https://doi.org/10.1186/s13048-025-01712-4 |
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| author | Yusi Luluk Rahmania Person Pesona Renta Damar Nurwahyu Bima Yu-Shan Lin Ngoc Thang Nguyen Pin-Yu Wang Meiny Suzery Wen-Tai Chiu |
| author_facet | Yusi Luluk Rahmania Person Pesona Renta Damar Nurwahyu Bima Yu-Shan Lin Ngoc Thang Nguyen Pin-Yu Wang Meiny Suzery Wen-Tai Chiu |
| author_sort | Yusi Luluk Rahmania |
| collection | DOAJ |
| description | Abstract Background Ovarian cancer is a highly prevalent cancer among women with a high risk for relapse and drug resistance. Seventy eight percent of women diagnosed with ovarian cancer live for at least one year after diagnosis. Hyptolide, a natural compound, has been shown to act as an anti-inflammatory and antibacterial agent, and latest research shows that it acts as an anticancer agent. These properties indicate that hyptolide may be a potential treatment option for ovarian cancer, including chemoresistant cases; however, its effects in chemoresistant ovarian cancer have not yet been demonstrated, and the mechanisms underlying its induction of cell death remain unclear. Results We found that hyptolide inhibited cell viability in ovarian cancer cell lines, regardless of their chemoresistance, and these effects were mediated by ER stress and the activation of GRP78 and ATF6. Combined treatment of cisplatin-resistant cell lines with hyptolide and cisplatin demonstrated a synergistic effect, enhancing apoptosis. Additionally, the reversal of chemoresistance with hyptolide treatment was mediated by β-catenin cytoplasm translocation leading to E-cadherin expression, ultimately promoting mesenchymal-epithelial transition. Conclusion Our findings suggest that hyptolide induces ER stress-mediated cell death and overcomes cisplatin chemoresistance in ovarian cancer cells, supporting its potential use as a chemotherapeutic agent. |
| format | Article |
| id | doaj-art-c1e4f34877384e6ca94a6636f3ac7b05 |
| institution | DOAJ |
| issn | 1757-2215 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Ovarian Research |
| spelling | doaj-art-c1e4f34877384e6ca94a6636f3ac7b052025-08-20T03:21:03ZengBMCJournal of Ovarian Research1757-22152025-06-0118111010.1186/s13048-025-01712-4Hyptolide induces ER stress-mediated cell death and enhances GSK3β-regulated cisplatin chemosensitivity in ovarian cancerYusi Luluk Rahmania0Person Pesona Renta1Damar Nurwahyu Bima2Yu-Shan Lin3Ngoc Thang Nguyen4Pin-Yu Wang5Meiny Suzery6Wen-Tai Chiu7Department of Biomedical Engineering, National Cheng Kung UniversityDepartment of Marine Science, Faculty of Agriculture, University of BengkuluDepartment of Chemistry, Faculty of Science and Mathematics, Diponegoro UniversityDepartment of Biomedical Engineering, National Cheng Kung UniversityDepartment of Biomedical Engineering, National Cheng Kung UniversityDepartment of Biomedical Engineering, National Cheng Kung UniversityDepartment of Chemistry, Faculty of Science and Mathematics, Diponegoro UniversityDepartment of Biomedical Engineering, National Cheng Kung UniversityAbstract Background Ovarian cancer is a highly prevalent cancer among women with a high risk for relapse and drug resistance. Seventy eight percent of women diagnosed with ovarian cancer live for at least one year after diagnosis. Hyptolide, a natural compound, has been shown to act as an anti-inflammatory and antibacterial agent, and latest research shows that it acts as an anticancer agent. These properties indicate that hyptolide may be a potential treatment option for ovarian cancer, including chemoresistant cases; however, its effects in chemoresistant ovarian cancer have not yet been demonstrated, and the mechanisms underlying its induction of cell death remain unclear. Results We found that hyptolide inhibited cell viability in ovarian cancer cell lines, regardless of their chemoresistance, and these effects were mediated by ER stress and the activation of GRP78 and ATF6. Combined treatment of cisplatin-resistant cell lines with hyptolide and cisplatin demonstrated a synergistic effect, enhancing apoptosis. Additionally, the reversal of chemoresistance with hyptolide treatment was mediated by β-catenin cytoplasm translocation leading to E-cadherin expression, ultimately promoting mesenchymal-epithelial transition. Conclusion Our findings suggest that hyptolide induces ER stress-mediated cell death and overcomes cisplatin chemoresistance in ovarian cancer cells, supporting its potential use as a chemotherapeutic agent.https://doi.org/10.1186/s13048-025-01712-4HyptolideOvarian cancerChemoresistantER stressGSK3ββ-catenin |
| spellingShingle | Yusi Luluk Rahmania Person Pesona Renta Damar Nurwahyu Bima Yu-Shan Lin Ngoc Thang Nguyen Pin-Yu Wang Meiny Suzery Wen-Tai Chiu Hyptolide induces ER stress-mediated cell death and enhances GSK3β-regulated cisplatin chemosensitivity in ovarian cancer Journal of Ovarian Research Hyptolide Ovarian cancer Chemoresistant ER stress GSK3β β-catenin |
| title | Hyptolide induces ER stress-mediated cell death and enhances GSK3β-regulated cisplatin chemosensitivity in ovarian cancer |
| title_full | Hyptolide induces ER stress-mediated cell death and enhances GSK3β-regulated cisplatin chemosensitivity in ovarian cancer |
| title_fullStr | Hyptolide induces ER stress-mediated cell death and enhances GSK3β-regulated cisplatin chemosensitivity in ovarian cancer |
| title_full_unstemmed | Hyptolide induces ER stress-mediated cell death and enhances GSK3β-regulated cisplatin chemosensitivity in ovarian cancer |
| title_short | Hyptolide induces ER stress-mediated cell death and enhances GSK3β-regulated cisplatin chemosensitivity in ovarian cancer |
| title_sort | hyptolide induces er stress mediated cell death and enhances gsk3β regulated cisplatin chemosensitivity in ovarian cancer |
| topic | Hyptolide Ovarian cancer Chemoresistant ER stress GSK3β β-catenin |
| url | https://doi.org/10.1186/s13048-025-01712-4 |
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