title: Raddeanoside R13 inhibits breast cancer cell proliferation, invasion, and metastasis.
abstract: Pulsatilla chinensis is one of the 50 famous fundamental herbs used in traditional Chinese medicine. Saponins are the main components of P. chinensis. Although the anti-proliferative function of saponins has been established in plenty types of cancer, the role of saponins on tumor invasion and metastasis has not been reported, and the mechanisms of how saponins exert the anti-tumor functions are still poorly characterized. Here, we demonstrate that, in breast cancer (BC) cells, raddeanoside R13, a component of saponins extracted from P. chinensis, exhibits strong anti-proliferative and anti-metastasis ability, accompanied by cell cycle arrest, apoptosis, autophagy, and reversion of epithelial-mesenchymal transition (EMT). Raddeanoside R13 (R13) inhibits BC cell proliferation via the activation of G1/S checkpoint transitions, concomitant with a marked decrease of the positive cell cycle regulators, including cyclin D1, cyclin A, and cyclin B1. R13 induces BC cell apoptosis accompanied by the increased levels of cleaved PARP and caspase-3. R13 inhibits BC cell migration and invasion and regulates the expression of the markers of EMT, which plays a critical role in cancer cell migration and invasion. Moreover, R13 suppresses BC tumor growth and metastasis in nude mice. These data highlight the important role of R13 in BC cell proliferation and progression and suggest that R13 may be a useful drug for BC therapy.
authors.affiliation: School of Chinese Materia Medica, Beijing University of Chinese Medicine, 6 Central Ring South Rd, Beijing, 100102, China.
authors.forename: Yingchun
authors.identifier: http://orcid.org/0000-0001-7876-0358
authors.initials: Y
authors.lastname: Liang
authors.affiliation: Department of Medical Molecular Biology, Beijing Institute of Biotechnology, 27 Tai-Ping Lu Rd, Beijing, 100850, People's Republic of China.|Jiangxi University of Traditional Chinese Medicine, Nanchang, China.
authors.forename: Xiaojie
authors.initials: X
authors.lastname: Xu
authors.affiliation: 401 Hospital of PLA Liberation Army, Qingdao, China.
authors.forename: Haiming
authors.initials: H
authors.lastname: Yu
authors.affiliation: Department of Medical Molecular Biology, Beijing Institute of Biotechnology, 27 Tai-Ping Lu Rd, Beijing, 100850, People's Republic of China.
authors.forename: Ling
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Medical Molecular Biology, Beijing Institute of Biotechnology, 27 Tai-Ping Lu Rd, Beijing, 100850, People's Republic of China.
authors.forename: Tian
authors.initials: T
authors.lastname: Hong
authors.affiliation: Department of Medical Molecular Biology, Beijing Institute of Biotechnology, 27 Tai-Ping Lu Rd, Beijing, 100850, People's Republic of China.
authors.forename: Quanbo
authors.initials: Q
authors.lastname: Ji
authors.affiliation: Jiangxi University of Traditional Chinese Medicine, Nanchang, China.
authors.forename: Yulin
authors.initials: Y
authors.lastname: Feng
authors.affiliation: Department of Medical Molecular Biology, Beijing Institute of Biotechnology, 27 Tai-Ping Lu Rd, Beijing, 100850, People's Republic of China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Jin
authors.affiliation: Department of Medical Molecular Biology, Beijing Institute of Biotechnology, 27 Tai-Ping Lu Rd, Beijing, 100850, People's Republic of China.
authors.forename: Yeqiong
authors.initials: Y
authors.lastname: Song
authors.affiliation: Department of Medical Molecular Biology, Beijing Institute of Biotechnology, 27 Tai-Ping Lu Rd, Beijing, 100850, People's Republic of China.
authors.forename: Jing
authors.initials: J
authors.lastname: Guo
authors.affiliation: Laboratory of Computer-aided Drug Design and Discovery, Beijing Institute of Pharmacology and Toxicology, Beijing, 100850, China. zzbcaptain@yahoo.com.cn.
authors.forename: Zhibing
authors.initials: Z
authors.lastname: Zheng
authors.affiliation: Department of Medical Molecular Biology, Beijing Institute of Biotechnology, 27 Tai-Ping Lu Rd, Beijing, 100850, People's Republic of China. yeqn66@yahoo.com.
authors.forename: Qinong
authors.initials: Q
authors.lastname: Ye
authors.affiliation: School of Chinese Materia Medica, Beijing University of Chinese Medicine, 6 Central Ring South Rd, Beijing, 100102, China. slyang3636@126.com.|Jiangxi University of Traditional Chinese Medicine, Nanchang, China. slyang3636@126.com.
authors.forename: Shilin
authors.initials: S
authors.lastname: Yang
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy / Q000187:drug effects; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D002453:Cell Cycle / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D005260:Female; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology*; D031946:Pulsatilla / Q000737:chemistry*; D012503:Saponins / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D010936:Plant Extracts; D012503:Saponins; C000614571:raddeanoside R13
keywords: Anti-tumor; Breast cancer; Cell proliferation; Invasion; Metastasis; Pulsatilla chinensis
references.citation: Int Immunopharmacol. 2010 May;10(5):584-90
references.pmid: 20159051
references.citation: Phytomedicine. 2012 Feb 15;19(3-4):293-300
references.pmid: 22001699
references.citation: Eur J Pharmacol. 2004 Sep 13;498(1-3):71-8
references.pmid: 15363977
references.citation: Cancer Sci. 2012 Nov;103(11):1929-37
references.pmid: 22909393
references.citation: Carcinogenesis. 2013 Sep;34(9):2156-69
references.pmid: 23671132
references.citation: Mol Cancer Ther. 2014 Mar;13(3):606-16
references.pmid: 24362463
references.citation: Biomed Res Int. 2015;2015:239764
references.pmid: 26339598
references.citation: Oncol Rep. 2013 Aug;30(2):801-8
references.pmid: 23733203
references.citation: J Ethnopharmacol. 2010 Apr 21;128(3):615-22
references.pmid: 20176097
references.citation: Phytomedicine. 2015 Sep 15;22(10):902-10
references.pmid: 26321739
references.citation: J Biol Chem. 1999 Aug 13;274(33):22932-40
references.pmid: 10438458
references.citation: Planta Med. 2002 Aug;68(8):672-5
references.pmid: 12221585
references.citation: J Surg Res. 2014 May 15;188(2):387-95
references.pmid: 24576780
references.citation: Phytochemistry. 1996 Jun;42(3):799-802
references.pmid: 8768325
references.citation: Food Chem. 2013 Jan 1;136(1):26-33
references.pmid: 23017388
references.citation: Cell Death Dis. 2013 Jul 11;4:e725
references.pmid: 23846227
references.citation: Environ Toxicol Pharmacol. 2015 Jul;40(1):30-8
references.pmid: 26056975
references.citation: Methods Mol Biol. 2012;928:221-8
references.pmid: 22956145
references.citation: Tumour Biol. 2014 Aug;35(8):7719-26
references.pmid: 24805829
references.citation: Anticancer Agents Med Chem. 2016;16(5):593-600
references.pmid: 26343144
references.citation: Sci Rep. 2013 Nov 14;3:3098
references.pmid: 24226295
references.citation: Tumour Biol. 2015 Aug;36(8):6295-304
references.pmid: 25854169
references.citation: Evid Based Complement Alternat Med. 2013;2013:517931
references.pmid: 24191167
references.citation: Dev Cell. 2004 Apr;6(4):463-77
references.pmid: 15068787
references.citation: Carcinogenesis. 2008 Oct;29(10):1885-92
references.pmid: 18586687
references.citation: Biochem J. 1997 Aug 15;326 ( Pt 1):1-16
references.pmid: 9337844