DICP OpenIR
Saikosaponin D from Radix Bupleuri suppresses triple-negative breast cancer cell growth by targeting beta-catenin signaling
Wang, Jixia1; Qi, Huan1; Zhang, Xiuli1,4; Si, Wei1; Xu, Fangfang1; Hou, Tao1; Zhou, Han1; Wang, Anhui2; Li, Guohui2; Liu, Yanfang1; Fang, Ye3; Piao, Hai-long1; Liang, Xinmiao1,4
Corresponding AuthorZhang, Xiuli(zhangxiuli@dicp.ac.cn) ; Piao, Hai-long(hpiao@dicp.ac.cn) ; Liang, Xinmiao(liangxm@dicp.ac.cn)
KeywordTriple-negative breast cancer Saikosaponin D Radix Bupleuri Wnt/beta-catenin
Source PublicationBIOMEDICINE & PHARMACOTHERAPY
2018-12-01
ISSN0753-3322
DOI10.1016/j.biopha.2018.09.038
Volume108Pages:724-733
Funding ProjectProject of International Cooperation Plan from Ministry of Science and Technology of the People's Republic of China[2015DFG32260] ; State Key Program Project of National Natural Science Foundation of China[U1508221] ; Project of National Natural Science Foundation of China[81473436] ; Project of National Natural Science Foundation of China[81403100] ; Project of National Natural Science Foundation of China[81672440] ; Creative Research Group Project of National Natural Science Foundation of China[21321064]
Funding OrganizationProject of International Cooperation Plan from Ministry of Science and Technology of the People's Republic of China ; Project of International Cooperation Plan from Ministry of Science and Technology of the People's Republic of China ; State Key Program Project of National Natural Science Foundation of China ; State Key Program Project of National Natural Science Foundation of China ; Project of National Natural Science Foundation of China ; Project of National Natural Science Foundation of China ; Creative Research Group Project of National Natural Science Foundation of China ; Creative Research Group Project of National Natural Science Foundation of China ; Project of International Cooperation Plan from Ministry of Science and Technology of the People's Republic of China ; Project of International Cooperation Plan from Ministry of Science and Technology of the People's Republic of China ; State Key Program Project of National Natural Science Foundation of China ; State Key Program Project of National Natural Science Foundation of China ; Project of National Natural Science Foundation of China ; Project of National Natural Science Foundation of China ; Creative Research Group Project of National Natural Science Foundation of China ; Creative Research Group Project of National Natural Science Foundation of China ; Project of International Cooperation Plan from Ministry of Science and Technology of the People's Republic of China ; Project of International Cooperation Plan from Ministry of Science and Technology of the People's Republic of China ; State Key Program Project of National Natural Science Foundation of China ; State Key Program Project of National Natural Science Foundation of China ; Project of National Natural Science Foundation of China ; Project of National Natural Science Foundation of China ; Creative Research Group Project of National Natural Science Foundation of China ; Creative Research Group Project of National Natural Science Foundation of China ; Project of International Cooperation Plan from Ministry of Science and Technology of the People's Republic of China ; Project of International Cooperation Plan from Ministry of Science and Technology of the People's Republic of China ; State Key Program Project of National Natural Science Foundation of China ; State Key Program Project of National Natural Science Foundation of China ; Project of National Natural Science Foundation of China ; Project of National Natural Science Foundation of China ; Creative Research Group Project of National Natural Science Foundation of China ; Creative Research Group Project of National Natural Science Foundation of China
WOS SubjectMedicine, Research & Experimental ; Pharmacology & Pharmacy
WOS Research AreaResearch & Experimental Medicine ; Pharmacology & Pharmacy
WOS KeywordD INHIBITS PROLIFERATION ; FACTOR RECEPTOR ; NEUROTENSIN RECEPTOR-1 ; CARCINOMA CELLS ; PROSTATE-CANCER ; MECHANISM ; APOPTOSIS ; CYCLOOXYGENASE-2 ; THERAPIES ; EXTRACTS
AbstractBackground: Triple-negative breast cancer (TNBC) is one of the most aggressive and poor prognosis breast cancers. Currently, chemotherapy with conventional cytotoxic agents is the only available option to treat TNBC. Hence, we identified new therapeutic agents against TNBC from traditional Chinese medicine Radix Bupleuri and unveiled the molecule mechanism of anti-TNBC effects. Methods: Multi-component bioactivity and structure-guided methods were used to identify the most effective anti-TNBC compound Saikosaponin D (SSD) from Radix Bupleuri. Cell viability and apoptosis assays were employed to demonstrate the effect of SSD on the proliferation and apoptosis of TNBC cells. Dynamic mass redistribution assay, TopFlash assay, western blotting, and special agonist were applied to dissect the potential molecular mechanisms of SSD. Results: We screened twenty fractions in Radix Bupleuri and identified SSD as the most effective component to inhibit the proliferation of TNBC cells. Investigating the interaction of SSD with the frequently overexpressed targets in TNBC led to the identification that it markedly suppressed Wnt/beta-catenin signaling, but did not act on epidermal growth factor receptor and neurotensin receptor-1. Moreover, we demonstrated that SSD significantly repressed beta-catenin and its downstream target genes, resulting in TNBC cell apoptosis. Specifically, docking of SSD to the crystal structure of beta-catenin suggested that SSD interacted with beta-catenin via hydrogen bonds and hydrophobic interaction. Conclusion: We identified the most effective component SSD from Radix Bupleuri in inhibiting the proliferation of TNBC cells by targeting beta-catenin signaling. Given the important role of Wnt/beta-catenin signaling in breast cancer, SSD may present an opportunity to discover new therapeutics for the treatment of TNBC.
Language英语
Funding OrganizationProject of International Cooperation Plan from Ministry of Science and Technology of the People's Republic of China ; Project of International Cooperation Plan from Ministry of Science and Technology of the People's Republic of China ; State Key Program Project of National Natural Science Foundation of China ; State Key Program Project of National Natural Science Foundation of China ; Project of National Natural Science Foundation of China ; Project of National Natural Science Foundation of China ; Creative Research Group Project of National Natural Science Foundation of China ; Creative Research Group Project of National Natural Science Foundation of China ; Project of International Cooperation Plan from Ministry of Science and Technology of the People's Republic of China ; Project of International Cooperation Plan from Ministry of Science and Technology of the People's Republic of China ; State Key Program Project of National Natural Science Foundation of China ; State Key Program Project of National Natural Science Foundation of China ; Project of National Natural Science Foundation of China ; Project of National Natural Science Foundation of China ; Creative Research Group Project of National Natural Science Foundation of China ; Creative Research Group Project of National Natural Science Foundation of China ; Project of International Cooperation Plan from Ministry of Science and Technology of the People's Republic of China ; Project of International Cooperation Plan from Ministry of Science and Technology of the People's Republic of China ; State Key Program Project of National Natural Science Foundation of China ; State Key Program Project of National Natural Science Foundation of China ; Project of National Natural Science Foundation of China ; Project of National Natural Science Foundation of China ; Creative Research Group Project of National Natural Science Foundation of China ; Creative Research Group Project of National Natural Science Foundation of China ; Project of International Cooperation Plan from Ministry of Science and Technology of the People's Republic of China ; Project of International Cooperation Plan from Ministry of Science and Technology of the People's Republic of China ; State Key Program Project of National Natural Science Foundation of China ; State Key Program Project of National Natural Science Foundation of China ; Project of National Natural Science Foundation of China ; Project of National Natural Science Foundation of China ; Creative Research Group Project of National Natural Science Foundation of China ; Creative Research Group Project of National Natural Science Foundation of China
WOS IDWOS:000450101800083
PublisherELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
Citation statistics
Cited Times:3[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://cas-ir.dicp.ac.cn/handle/321008/166659
Collection中国科学院大连化学物理研究所
Corresponding AuthorZhang, Xiuli; Piao, Hai-long; Liang, Xinmiao
Affiliation1.Chinese Acad Sci, Dalian Inst Chem Phys, CAS Key Lab Separat Sci Analyt Chem, Dalian 116023, Peoples R China
2.Chinese Acad Sci, Dalian Inst Chem Phys, Lab Mol Modeling & Design, State Key Lab Mol React Dynam, Dalian 116023, Peoples R China
3.Corning, Biochem Technol, Div Sci & Technol, Corning, NY 14831 USA
4.Nantong Univ, Coinnovat Ctr Neuroregenerat, Nantong 226019, Peoples R China
Recommended Citation
GB/T 7714
Wang, Jixia,Qi, Huan,Zhang, Xiuli,et al. Saikosaponin D from Radix Bupleuri suppresses triple-negative breast cancer cell growth by targeting beta-catenin signaling[J]. BIOMEDICINE & PHARMACOTHERAPY,2018,108:724-733.
APA Wang, Jixia.,Qi, Huan.,Zhang, Xiuli.,Si, Wei.,Xu, Fangfang.,...&Liang, Xinmiao.(2018).Saikosaponin D from Radix Bupleuri suppresses triple-negative breast cancer cell growth by targeting beta-catenin signaling.BIOMEDICINE & PHARMACOTHERAPY,108,724-733.
MLA Wang, Jixia,et al."Saikosaponin D from Radix Bupleuri suppresses triple-negative breast cancer cell growth by targeting beta-catenin signaling".BIOMEDICINE & PHARMACOTHERAPY 108(2018):724-733.
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