Senkyunolide H reverses depression-induced breast cancer progression by regulating CXCR2

doi:10.1007/s13659-025-00543-6

Natural Products and Bioprospecting ›› 2025, Vol. 15 ›› Issue (6): 57-57.DOI: 10.1007/s13659-025-00543-6

• Original Article • Previous Articles Next Articles

Senkyunolide H reverses depression-induced breast cancer progression by regulating CXCR2

Yingchao Wu^1,2,3,4, Jiaqi Cui⁵, Liushan Chen^1,2,3, Jieting Chen^1,3, Junfeng Huang⁶, Congwen Yang^1,3,4, Yuqi Liang^1,2,3, Qianjun Chen^1,2,3, Qian Zuo^1,2,3

1. Chinese Medicine Guangdong Laboratory, Hengqin, 519031, Guangdong, China;
2. State Key Laboratory of Traditional Chinese Medicine Syndrome, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510006, Guangdong, China;
3. Department of Breast, Guangdong Provincial Hospital of Chinese Medicine, 111 Dade Road, Guangzhou, 510006, Guangdong, China;
4. The Second Clinical College of Guangzhou, University of Chinese Medicine, Guangzhou, 510006, Guangdong, China;
5. College of Traditional Chinese Medicine, Jinan University, Guangzhou, 510405, Guangdong, China;
6. The First Clinical College of Guangzhou, University of Chinese Medicine, Guangzhou, 510405, Guangdong, China

Received:2025-05-06 Online:2026-01-12
Contact: Qianjun Chen Email:E-mail:cqj55@163.com
Supported by:
This work was supported by the National Natural Science Foundation of China (82274513, 82305234 and 82474504), the Guangdong Basic and Applied Basic Research Foundation (2023A1515011115), the Incubation Program for the Science and Technology Development of Chinese Medicine Guangdong Laboratory (HQL2024PZ023), the Planned Science Technology Project of Guangzhou (SL2023A03J01120, SL2023A04J00228, and 2024A03J0850), the Project of Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome (YN2023ZH10), the Autonomous Project of State Key Laboratory of Traditional Chinese Medicine Syndrome (QZ2023ZZ13), the Beijing Medical Foundation (MDK2023-1007), and the Science and Technology Innovation Medical Development Foundation of Beijing (KC2023-JX-0082-12).

Senkyunolide H reverses depression-induced breast cancer progression by regulating CXCR2

Yingchao Wu^1,2,3,4, Jiaqi Cui⁵, Liushan Chen^1,2,3, Jieting Chen^1,3, Junfeng Huang⁶, Congwen Yang^1,3,4, Yuqi Liang^1,2,3, Qianjun Chen^1,2,3, Qian Zuo^1,2,3

1. Chinese Medicine Guangdong Laboratory, Hengqin, 519031, Guangdong, China;
2. State Key Laboratory of Traditional Chinese Medicine Syndrome, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510006, Guangdong, China;
3. Department of Breast, Guangdong Provincial Hospital of Chinese Medicine, 111 Dade Road, Guangzhou, 510006, Guangdong, China;
4. The Second Clinical College of Guangzhou, University of Chinese Medicine, Guangzhou, 510006, Guangdong, China;
5. College of Traditional Chinese Medicine, Jinan University, Guangzhou, 510405, Guangdong, China;
6. The First Clinical College of Guangzhou, University of Chinese Medicine, Guangzhou, 510405, Guangdong, China

通讯作者: Qianjun Chen Email:E-mail:cqj55@163.com
作者简介:Qian Zuo Email:E-mail:827649822@qq.com
基金资助:
This work was supported by the National Natural Science Foundation of China (82274513, 82305234 and 82474504), the Guangdong Basic and Applied Basic Research Foundation (2023A1515011115), the Incubation Program for the Science and Technology Development of Chinese Medicine Guangdong Laboratory (HQL2024PZ023), the Planned Science Technology Project of Guangzhou (SL2023A03J01120, SL2023A04J00228, and 2024A03J0850), the Project of Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome (YN2023ZH10), the Autonomous Project of State Key Laboratory of Traditional Chinese Medicine Syndrome (QZ2023ZZ13), the Beijing Medical Foundation (MDK2023-1007), and the Science and Technology Innovation Medical Development Foundation of Beijing (KC2023-JX-0082-12).

Abstract

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.

Key words: Breast cancer, Depression, IL-8, CXCR2, Senkyunolide H

摘要： 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.

关键词: Breast cancer, Depression, IL-8, CXCR2, Senkyunolide H

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[J]. Natural Products and Bioprospecting, 2025, 15(6): 57-57.

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Senkyunolide H reverses depression-induced breast cancer progression by regulating CXCR2

Senkyunolide H reverses depression-induced breast cancer progression by regulating CXCR2

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