Senkyunolide H reverses depression-induced breast cancer progression by regulating CXCR2
Abstract Background Depression promotes breast cancer progression. Given the lack of specific targets for depression-associated breast cancer, there are currently no therapeutic drugs for this type of breast cancer. Methods Transcriptomic analysis was conducted to identify and functionally annotate...
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| Format: | Article |
| Language: | English |
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SpringerOpen
2025-08-01
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| Series: | Natural Products and Bioprospecting |
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| Online Access: | https://doi.org/10.1007/s13659-025-00543-6 |
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| author | Yingchao Wu Jiaqi Cui Liushan Chen Jieting Chen Junfeng Huang Congwen Yang Yuqi Liang Qianjun Chen Qian Zuo |
| author_facet | Yingchao Wu Jiaqi Cui Liushan Chen Jieting Chen Junfeng Huang Congwen Yang Yuqi Liang Qianjun Chen Qian Zuo |
| author_sort | Yingchao Wu |
| collection | DOAJ |
| description | Abstract Background Depression promotes breast cancer progression. Given the lack of specific targets for depression-associated breast cancer, there are currently no therapeutic drugs for this type of breast cancer. Methods Transcriptomic analysis was conducted to identify and functionally annotate genes with differential expression in breast cancer patients exhibiting depressive symptoms. Subsequently, Mendelian randomization was employed to investigate the causal associations between these pivotal genes and breast cancer, thereby validating their potential roles as therapeutic targets. Furthermore, molecular docking techniques were utilized to screen for candidate compounds that may exert therapeutic effects on depression-associated breast cancer. The efficacy of the selected compounds was further assessed using both in vitro cellular experiments and in vivo animal models. Results We identified IL-8 as a key gene involved in depression-mediated breast cancer progression using transcriptomics. Mendelian randomized analysis suggested that high IL-8 expression promoted breast cancer progression. Further studies demonstrated that IL-8 mediated the breast cancer-promoting effect of depression through the receptor CXCR2. Evidence from both in vitro and in vivo experiments indicates that senkyunolide H may exert its therapeutic effect by regulating CXCR2, thereby counteracting the protumor effects associated with depression in breast cancer. Conclusion Depression activates CXCR2-mediated breast cancer cell proliferation through IL-8, and senkyunolide H regulates CXCR2 and inhibits its ability to block the cancer-promoting effects of depression, ultimately inhibiting the growth of breast cancer in the context of depression. Graphical Abstract |
| format | Article |
| id | doaj-art-111b770f764c4205ae3e6e33ab63ef17 |
| institution | Kabale University |
| issn | 2192-2195 2192-2209 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | SpringerOpen |
| record_format | Article |
| series | Natural Products and Bioprospecting |
| spelling | doaj-art-111b770f764c4205ae3e6e33ab63ef172025-08-24T11:57:23ZengSpringerOpenNatural Products and Bioprospecting2192-21952192-22092025-08-0115111510.1007/s13659-025-00543-6Senkyunolide H reverses depression-induced breast cancer progression by regulating CXCR2Yingchao Wu0Jiaqi Cui1Liushan Chen2Jieting Chen3Junfeng Huang4Congwen Yang5Yuqi Liang6Qianjun Chen7Qian Zuo8Chinese Medicine Guangdong LaboratoryCollege of Traditional Chinese Medicine, Jinan UniversityChinese Medicine Guangdong LaboratoryChinese Medicine Guangdong LaboratoryThe First Clinical College of Guangzhou, University of Chinese MedicineChinese Medicine Guangdong LaboratoryChinese Medicine Guangdong LaboratoryChinese Medicine Guangdong LaboratoryChinese Medicine Guangdong LaboratoryAbstract Background Depression promotes breast cancer progression. Given the lack of specific targets for depression-associated breast cancer, there are currently no therapeutic drugs for this type of breast cancer. Methods Transcriptomic analysis was conducted to identify and functionally annotate genes with differential expression in breast cancer patients exhibiting depressive symptoms. Subsequently, Mendelian randomization was employed to investigate the causal associations between these pivotal genes and breast cancer, thereby validating their potential roles as therapeutic targets. Furthermore, molecular docking techniques were utilized to screen for candidate compounds that may exert therapeutic effects on depression-associated breast cancer. The efficacy of the selected compounds was further assessed using both in vitro cellular experiments and in vivo animal models. Results We identified IL-8 as a key gene involved in depression-mediated breast cancer progression using transcriptomics. Mendelian randomized analysis suggested that high IL-8 expression promoted breast cancer progression. Further studies demonstrated that IL-8 mediated the breast cancer-promoting effect of depression through the receptor CXCR2. Evidence from both in vitro and in vivo experiments indicates that senkyunolide H may exert its therapeutic effect by regulating CXCR2, thereby counteracting the protumor effects associated with depression in breast cancer. Conclusion Depression activates CXCR2-mediated breast cancer cell proliferation through IL-8, and senkyunolide H regulates CXCR2 and inhibits its ability to block the cancer-promoting effects of depression, ultimately inhibiting the growth of breast cancer in the context of depression. Graphical Abstracthttps://doi.org/10.1007/s13659-025-00543-6Breast cancerDepressionIL-8CXCR2Senkyunolide H |
| spellingShingle | Yingchao Wu Jiaqi Cui Liushan Chen Jieting Chen Junfeng Huang Congwen Yang Yuqi Liang Qianjun Chen Qian Zuo Senkyunolide H reverses depression-induced breast cancer progression by regulating CXCR2 Natural Products and Bioprospecting Breast cancer Depression IL-8 CXCR2 Senkyunolide H |
| title | Senkyunolide H reverses depression-induced breast cancer progression by regulating CXCR2 |
| title_full | Senkyunolide H reverses depression-induced breast cancer progression by regulating CXCR2 |
| title_fullStr | Senkyunolide H reverses depression-induced breast cancer progression by regulating CXCR2 |
| title_full_unstemmed | Senkyunolide H reverses depression-induced breast cancer progression by regulating CXCR2 |
| title_short | Senkyunolide H reverses depression-induced breast cancer progression by regulating CXCR2 |
| title_sort | senkyunolide h reverses depression induced breast cancer progression by regulating cxcr2 |
| topic | Breast cancer Depression IL-8 CXCR2 Senkyunolide H |
| url | https://doi.org/10.1007/s13659-025-00543-6 |
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