Sanguinarine chloride induces ferroptosis by regulating ROS/BACH1/HMOX1 signaling pathway in prostate cancer
Abstract Background Sanguinarine chloride (S.C) is a benzophenanthrine alkaloid derived from the root of sanguinaria canadensis and other poppy-fumaria species. Studies have reported that S.C exhibits antioxidant, anti-inflammatory, proapoptotic, and growth inhibitory effects, which contribute to it...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2024-01-01
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| Series: | Chinese Medicine |
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| Online Access: | https://doi.org/10.1186/s13020-024-00881-6 |
| _version_ | 1797355501446496256 |
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| author | Shanhui Liu Yan Tao Shan Wu Jiawei Lin Shengjun Fu Jianzhong Lu Jing Zhang Beitang Fu Erdong Zhang Jing Xu Jiaxuan Wang Lanlan Li Lei Zhang Zhiping Wang |
| author_facet | Shanhui Liu Yan Tao Shan Wu Jiawei Lin Shengjun Fu Jianzhong Lu Jing Zhang Beitang Fu Erdong Zhang Jing Xu Jiaxuan Wang Lanlan Li Lei Zhang Zhiping Wang |
| author_sort | Shanhui Liu |
| collection | DOAJ |
| description | Abstract Background Sanguinarine chloride (S.C) is a benzophenanthrine alkaloid derived from the root of sanguinaria canadensis and other poppy-fumaria species. Studies have reported that S.C exhibits antioxidant, anti-inflammatory, proapoptotic, and growth inhibitory effects, which contribute to its anti-cancer properties. Recent studies suggested that the antitumor effect of S.C through inducing ferroptosis in some cancers. Nevertheless, the precise mechanism underlying the regulation of ferroptosis by S.C remains poorly understood. Methods A small molecule library was constructed based on FDA and CFDA approved small molecular drugs. CCK-8 assay was applied to evaluate the effects of the small molecule compound on tumor cell viability. Prostate cancer cells were treated with S.C and then the cell viability and migration ability were assessed using CCK8, colony formation and wound healing assay. Reactive oxygen species (ROS) and iron accumulation were quantified through flow cytometry analysis. The levels of malondialdehyde (MDA) and total glutathione (GSH) were measured using commercially available kits. RNA-seq analysis was performed to identify differentially expressed genes (DEGs) among the treatment groups. Western blotting and qPCR were utilized to investigate the expression of relevant proteins and genes. In vivo experiments employed a xenograft mice model to evaluate the anti-cancer efficacy of S.C. Results Our study demonstrated that S.C effectively inhibited the viability of various prostate cancer cells. Notably, S.C exhibited the ability to enhance the cytotoxicity of docetaxel in DU145 cells. We found that S.C-induced cell death partially relied on the induction of ferroptosis, which was mediated through up-regulation of HMOX1 protein. Additionally, our investigation revealed that S.C treatment decreased the stability of BACH1 protein, which contributed to HMOX1expression. We further identified that S.C-induced ROS caused BACH1 instability by suppressing USP47expression. Moreover, In DU145 xenograft model, we found S.C significantly inhibited prostate cancer growth, highlighting its potential as a therapeutic strategy. Collectively, these findings provide evidence that S.C could induce regulated cell death (RCD) in prostate cancer cells and effectively inhibit tumor growth via triggering ferroptosis. This study provides evidence that S.C effectively suppresses tumor progression and induces ferroptosis in prostate cancer cells by targeting ROS/USP47/BACH1/HMOX1 axis. Conclusion This study provides evidence that S.C effectively suppresses tumor progression and induces ferroptosis in prostate cancer cells by targeting the ROS/USP47/BACH1/HMOX1 axis. These findings offer novel insights into the underlying mechanism by which S.C inhibits the progression of prostate cancer. Furthermore, leveraging the potential of S.C in targeting ferroptosis may present a new therapeutic opportunity for prostate cancer. This study found that S.C induces ferroptosis by targeting the ROS/USP47/BACH1/HMOX1 axis in prostate cancer cells. Graphical Abstract |
| first_indexed | 2024-03-08T14:12:05Z |
| format | Article |
| id | doaj.art-5686950e7e9046709c56a696a984f4d6 |
| institution | Directory Open Access Journal |
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| language | English |
| last_indexed | 2024-03-08T14:12:05Z |
| publishDate | 2024-01-01 |
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| series | Chinese Medicine |
| spelling | doaj.art-5686950e7e9046709c56a696a984f4d62024-01-14T12:36:28ZengBMCChinese Medicine1749-85462024-01-0119111810.1186/s13020-024-00881-6Sanguinarine chloride induces ferroptosis by regulating ROS/BACH1/HMOX1 signaling pathway in prostate cancerShanhui Liu0Yan Tao1Shan Wu2Jiawei Lin3Shengjun Fu4Jianzhong Lu5Jing Zhang6Beitang Fu7Erdong Zhang8Jing Xu9Jiaxuan Wang10Lanlan Li11Lei Zhang12Zhiping Wang13Institute of Urology, Clinical Research Center for Urology in Gansu Province, Key Laboratory of Urological Disease in Gansu Province, Lanzhou University Second HospitalInstitute of Urology, Clinical Research Center for Urology in Gansu Province, Key Laboratory of Urological Disease in Gansu Province, Lanzhou University Second HospitalGansu Provincial Center for Disease Control and PreventionCyrus Tang Hematology Center, Collaborative Innovation Center of Hematology, National Clinical Research Center for Hematologic Diseases, Soochow UniversityInstitute of Urology, Clinical Research Center for Urology in Gansu Province, Key Laboratory of Urological Disease in Gansu Province, Lanzhou University Second HospitalInstitute of Urology, Clinical Research Center for Urology in Gansu Province, Key Laboratory of Urological Disease in Gansu Province, Lanzhou University Second HospitalInstitute of Urology, Clinical Research Center for Urology in Gansu Province, Key Laboratory of Urological Disease in Gansu Province, Lanzhou University Second HospitalThe Fifth Affiliated Hospital of Xinjiang Medical UniversityKey Laboratory of Optimal Utilization of Natural Medicinal Resources, Guizhou Medical UniversityThe Second Clinical Medical College of Lanzhou University, Lanzhou UniversityThe Second Clinical Medical College of Lanzhou University, Lanzhou UniversityInstitute of Urology, Clinical Research Center for Urology in Gansu Province, Key Laboratory of Urological Disease in Gansu Province, Lanzhou University Second HospitalCyrus Tang Hematology Center, Collaborative Innovation Center of Hematology, National Clinical Research Center for Hematologic Diseases, Soochow UniversityInstitute of Urology, Clinical Research Center for Urology in Gansu Province, Key Laboratory of Urological Disease in Gansu Province, Lanzhou University Second HospitalAbstract Background Sanguinarine chloride (S.C) is a benzophenanthrine alkaloid derived from the root of sanguinaria canadensis and other poppy-fumaria species. Studies have reported that S.C exhibits antioxidant, anti-inflammatory, proapoptotic, and growth inhibitory effects, which contribute to its anti-cancer properties. Recent studies suggested that the antitumor effect of S.C through inducing ferroptosis in some cancers. Nevertheless, the precise mechanism underlying the regulation of ferroptosis by S.C remains poorly understood. Methods A small molecule library was constructed based on FDA and CFDA approved small molecular drugs. CCK-8 assay was applied to evaluate the effects of the small molecule compound on tumor cell viability. Prostate cancer cells were treated with S.C and then the cell viability and migration ability were assessed using CCK8, colony formation and wound healing assay. Reactive oxygen species (ROS) and iron accumulation were quantified through flow cytometry analysis. The levels of malondialdehyde (MDA) and total glutathione (GSH) were measured using commercially available kits. RNA-seq analysis was performed to identify differentially expressed genes (DEGs) among the treatment groups. Western blotting and qPCR were utilized to investigate the expression of relevant proteins and genes. In vivo experiments employed a xenograft mice model to evaluate the anti-cancer efficacy of S.C. Results Our study demonstrated that S.C effectively inhibited the viability of various prostate cancer cells. Notably, S.C exhibited the ability to enhance the cytotoxicity of docetaxel in DU145 cells. We found that S.C-induced cell death partially relied on the induction of ferroptosis, which was mediated through up-regulation of HMOX1 protein. Additionally, our investigation revealed that S.C treatment decreased the stability of BACH1 protein, which contributed to HMOX1expression. We further identified that S.C-induced ROS caused BACH1 instability by suppressing USP47expression. Moreover, In DU145 xenograft model, we found S.C significantly inhibited prostate cancer growth, highlighting its potential as a therapeutic strategy. Collectively, these findings provide evidence that S.C could induce regulated cell death (RCD) in prostate cancer cells and effectively inhibit tumor growth via triggering ferroptosis. This study provides evidence that S.C effectively suppresses tumor progression and induces ferroptosis in prostate cancer cells by targeting ROS/USP47/BACH1/HMOX1 axis. Conclusion This study provides evidence that S.C effectively suppresses tumor progression and induces ferroptosis in prostate cancer cells by targeting the ROS/USP47/BACH1/HMOX1 axis. These findings offer novel insights into the underlying mechanism by which S.C inhibits the progression of prostate cancer. Furthermore, leveraging the potential of S.C in targeting ferroptosis may present a new therapeutic opportunity for prostate cancer. This study found that S.C induces ferroptosis by targeting the ROS/USP47/BACH1/HMOX1 axis in prostate cancer cells. Graphical Abstracthttps://doi.org/10.1186/s13020-024-00881-6FerroptosisSanguinarine chlorideProstate cancerHMOX1BACH1 |
| spellingShingle | Shanhui Liu Yan Tao Shan Wu Jiawei Lin Shengjun Fu Jianzhong Lu Jing Zhang Beitang Fu Erdong Zhang Jing Xu Jiaxuan Wang Lanlan Li Lei Zhang Zhiping Wang Sanguinarine chloride induces ferroptosis by regulating ROS/BACH1/HMOX1 signaling pathway in prostate cancer Chinese Medicine Ferroptosis Sanguinarine chloride Prostate cancer HMOX1 BACH1 |
| title | Sanguinarine chloride induces ferroptosis by regulating ROS/BACH1/HMOX1 signaling pathway in prostate cancer |
| title_full | Sanguinarine chloride induces ferroptosis by regulating ROS/BACH1/HMOX1 signaling pathway in prostate cancer |
| title_fullStr | Sanguinarine chloride induces ferroptosis by regulating ROS/BACH1/HMOX1 signaling pathway in prostate cancer |
| title_full_unstemmed | Sanguinarine chloride induces ferroptosis by regulating ROS/BACH1/HMOX1 signaling pathway in prostate cancer |
| title_short | Sanguinarine chloride induces ferroptosis by regulating ROS/BACH1/HMOX1 signaling pathway in prostate cancer |
| title_sort | sanguinarine chloride induces ferroptosis by regulating ros bach1 hmox1 signaling pathway in prostate cancer |
| topic | Ferroptosis Sanguinarine chloride Prostate cancer HMOX1 BACH1 |
| url | https://doi.org/10.1186/s13020-024-00881-6 |
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