Saikosaponin A induces cellular senescence in triple-negative breast cancer by inhibiting the PI3K/Akt signalling pathway
BackgroundBreast cancer has now become the most prevalent cancer worldwide. Existing therapeutic agents are generally accompanied by significant side effects. Here, we highlight Saikosaponin A (SSA), a promising natural metabolite characterized by low toxicity, demonstrating significant efficacy aga...
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Frontiers Media S.A.
2025-04-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2025.1532579/full |
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| author | Yingchao Wu Yingchao Wu Liushan Chen Liushan Chen Liushan Chen Liushan Chen Dajin Pi Jiaqi Cui Yuqi Liang Yuqi Liang Yuqi Liang Yuqi Liang Peng Wu Mingzi Ouyang Qian Zuo Qian Zuo Qian Zuo Qian Zuo |
| author_facet | Yingchao Wu Yingchao Wu Liushan Chen Liushan Chen Liushan Chen Liushan Chen Dajin Pi Jiaqi Cui Yuqi Liang Yuqi Liang Yuqi Liang Yuqi Liang Peng Wu Mingzi Ouyang Qian Zuo Qian Zuo Qian Zuo Qian Zuo |
| author_sort | Yingchao Wu |
| collection | DOAJ |
| description | BackgroundBreast cancer has now become the most prevalent cancer worldwide. Existing therapeutic agents are generally accompanied by significant side effects. Here, we highlight Saikosaponin A (SSA), a promising natural metabolite characterized by low toxicity, demonstrating significant efficacy against breast cancer through the induction of cellular senescence.MethodsThe antitumor property of SSA was determined via MTT colorimetric assay, 5-ethynyl-2′-deoxyuridine (EdU) incorporation assay, colony formation, and propidium iodide (PI) staining in vitro, as well as xenograft in vivo model. A network approach was used to predict potential targets of SSA reevant for a potential anti-tumor effect and verified through senescence-associated β-galactosidase (SA-β-gal), flow-cytometry analysis, RT-PCR, Western blotting, and immuno-histochemistry assay.ResultsSSA significantly suppressed proliferation and triggered cell cycle arrest of SUM159PT and MDA-MB-231 cells. Revealed by network analysis, cellular senescence, and phosphatidylinositol-3-kinase (PI3K)/Akt signaling pathway were implemented in the anti-tumor effects of SSA. SSA-stimulated senescence was associated with increased ROS production, distinct senescence-associated secretory phenotype (SASP), and restricted PI3K/Akt signaling, as well as p21 and p53 accumulation. Furthermore, SSA displayed inhibitory effects on tumor growth with minimal toxicity in animal studies, accompanied by activated biomarkers of cellular senescence and decreased expression of p-Akt and p-PI3K.ConclusionTaken together, based on the preliminary results of network analysis and further experimental validation, this study revealed that SSA significantly induced cell cycle arrest and senescence, and the inhibition of ROS-mediated PI3K/Akt pathway may be the potential mechanism in this process. |
| format | Article |
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| institution | OA Journals |
| issn | 1663-9812 |
| language | English |
| publishDate | 2025-04-01 |
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| spelling | doaj-art-ea4ff7b9f7f9429e90ecf1c0b465572e2025-08-20T02:18:34ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-04-011610.3389/fphar.2025.15325791532579Saikosaponin A induces cellular senescence in triple-negative breast cancer by inhibiting the PI3K/Akt signalling pathwayYingchao Wu0Yingchao Wu1Liushan Chen2Liushan Chen3Liushan Chen4Liushan Chen5Dajin Pi6Jiaqi Cui7Yuqi Liang8Yuqi Liang9Yuqi Liang10Yuqi Liang11Peng Wu12Mingzi Ouyang13Qian Zuo14Qian Zuo15Qian Zuo16Qian Zuo17State Key Laboratory of Traditional Chinese Medicine Syndrome, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, ChinaThe Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, ChinaState Key Laboratory of Traditional Chinese Medicine Syndrome, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, ChinaDepartment of Breast, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, Guangdong, ChinaGuangdong Academy of Traditional Chinese Medicine, Guangzhou, Guangdong, ChinaGuangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, Guangzhou, Guangdong, ChinaSchool of Traditional Chinese Medicine, Jinan University, Guangzhou, Guangdong, ChinaSchool of Traditional Chinese Medicine, Jinan University, Guangzhou, Guangdong, ChinaState Key Laboratory of Traditional Chinese Medicine Syndrome, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, ChinaDepartment of Breast, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, Guangdong, ChinaGuangdong Academy of Traditional Chinese Medicine, Guangzhou, Guangdong, ChinaGuangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, Guangzhou, Guangdong, ChinaThe Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, ChinaSchool of Traditional Chinese Medicine, Jinan University, Guangzhou, Guangdong, ChinaState Key Laboratory of Traditional Chinese Medicine Syndrome, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, ChinaDepartment of Breast, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, Guangdong, ChinaGuangdong Academy of Traditional Chinese Medicine, Guangzhou, Guangdong, ChinaGuangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, Guangzhou, Guangdong, ChinaBackgroundBreast cancer has now become the most prevalent cancer worldwide. Existing therapeutic agents are generally accompanied by significant side effects. Here, we highlight Saikosaponin A (SSA), a promising natural metabolite characterized by low toxicity, demonstrating significant efficacy against breast cancer through the induction of cellular senescence.MethodsThe antitumor property of SSA was determined via MTT colorimetric assay, 5-ethynyl-2′-deoxyuridine (EdU) incorporation assay, colony formation, and propidium iodide (PI) staining in vitro, as well as xenograft in vivo model. A network approach was used to predict potential targets of SSA reevant for a potential anti-tumor effect and verified through senescence-associated β-galactosidase (SA-β-gal), flow-cytometry analysis, RT-PCR, Western blotting, and immuno-histochemistry assay.ResultsSSA significantly suppressed proliferation and triggered cell cycle arrest of SUM159PT and MDA-MB-231 cells. Revealed by network analysis, cellular senescence, and phosphatidylinositol-3-kinase (PI3K)/Akt signaling pathway were implemented in the anti-tumor effects of SSA. SSA-stimulated senescence was associated with increased ROS production, distinct senescence-associated secretory phenotype (SASP), and restricted PI3K/Akt signaling, as well as p21 and p53 accumulation. Furthermore, SSA displayed inhibitory effects on tumor growth with minimal toxicity in animal studies, accompanied by activated biomarkers of cellular senescence and decreased expression of p-Akt and p-PI3K.ConclusionTaken together, based on the preliminary results of network analysis and further experimental validation, this study revealed that SSA significantly induced cell cycle arrest and senescence, and the inhibition of ROS-mediated PI3K/Akt pathway may be the potential mechanism in this process.https://www.frontiersin.org/articles/10.3389/fphar.2025.1532579/fullsaikosaponin abreast cancernetwork analysiscellular senescencePI3K/Akt signaling pathway |
| spellingShingle | Yingchao Wu Yingchao Wu Liushan Chen Liushan Chen Liushan Chen Liushan Chen Dajin Pi Jiaqi Cui Yuqi Liang Yuqi Liang Yuqi Liang Yuqi Liang Peng Wu Mingzi Ouyang Qian Zuo Qian Zuo Qian Zuo Qian Zuo Saikosaponin A induces cellular senescence in triple-negative breast cancer by inhibiting the PI3K/Akt signalling pathway Frontiers in Pharmacology saikosaponin a breast cancer network analysis cellular senescence PI3K/Akt signaling pathway |
| title | Saikosaponin A induces cellular senescence in triple-negative breast cancer by inhibiting the PI3K/Akt signalling pathway |
| title_full | Saikosaponin A induces cellular senescence in triple-negative breast cancer by inhibiting the PI3K/Akt signalling pathway |
| title_fullStr | Saikosaponin A induces cellular senescence in triple-negative breast cancer by inhibiting the PI3K/Akt signalling pathway |
| title_full_unstemmed | Saikosaponin A induces cellular senescence in triple-negative breast cancer by inhibiting the PI3K/Akt signalling pathway |
| title_short | Saikosaponin A induces cellular senescence in triple-negative breast cancer by inhibiting the PI3K/Akt signalling pathway |
| title_sort | saikosaponin a induces cellular senescence in triple negative breast cancer by inhibiting the pi3k akt signalling pathway |
| topic | saikosaponin a breast cancer network analysis cellular senescence PI3K/Akt signaling pathway |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2025.1532579/full |
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