Saikosaponin D from Radix Bupleuri suppresses triple-negative breast cancer cell growth by targeting beta-catenin signaling

doi:10.1016/j.biopha.2018.09.038

	Saikosaponin D from Radix Bupleuri suppresses triple-negative breast cancer cell growth by targeting beta-catenin signaling
	Wang, Jixia 1; Qi, Huan 1; Zhang, Xiuli 1,4; Si, Wei 1; Xu, Fangfang 1; Hou, Tao 1; Zhou, Han 1; Wang, Anhui 2; Li, Guohui 2; Liu, Yanfang 1
刊名	BIOMEDICINE & PHARMACOTHERAPY
	2018-12-01
卷号	108 页码:724-733
关键词	Triple-negative breast cancer Saikosaponin D Radix Bupleuri Wnt/beta-catenin
ISSN号	0753-3322
DOI	10.1016/j.biopha.2018.09.038
通讯作者	Zhang, Xiuli(zhangxiuli@dicp.ac.cn) ; Piao, Hai-long(hpiao@dicp.ac.cn) ; Liang, Xinmiao(liangxm@dicp.ac.cn)
英文摘要	Background: 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.
资助项目	Project 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]
WOS关键词	D INHIBITS PROLIFERATION ; FACTOR RECEPTOR ; NEUROTENSIN RECEPTOR-1 ; CARCINOMA CELLS ; PROSTATE-CANCER ; MECHANISM ; APOPTOSIS ; CYCLOOXYGENASE-2 ; THERAPIES ; EXTRACTS
WOS研究方向	Research & Experimental Medicine ; Pharmacology & Pharmacy
语种	英语
出版者	ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
WOS记录号	WOS:000450101800083
资助机构	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 ; 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
内容类型	期刊论文
源URL	[http://cas-ir.dicp.ac.cn/handle/321008/166658]
专题	大连化学物理研究所_中国科学院大连化学物理研究所
通讯作者	Zhang, Xiuli; Piao, Hai-long; Liang, Xinmiao
作者单位	1.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
推荐引用方式 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.