title: The apoptotic effect of D Rhamnose β-hederin, a novel oleanane-type triterpenoid saponin on breast cancer cells.
abstract: There is growing interest in development of natural products as anti-cancer and chemopreventive agents. Many triterpenoids have been proved as potential agents for chemoprevention and therapy of breast cancer. Ginsenosides from ginseng, which mostly belong to dammarane-type triterpenoids, have gained great attention for their anti-breast cancer activity with diverse mechanisms. However, studies of other kinds of triterpenoid saponins on breast cancer are limited. Previously, we purified and identified a novel oleanane-type triterpene saponin named D Rhamnose β-hederin (DRβ-H) from Clematis ganpiniana, a Chinese traditional anti-tumor herb. In the present study, DRβ-H showed strong inhibitory activity on the growth of various breast cancer cells and induced apoptosis in these cells. DRβ-H inhibited PI3K/AKT and activated ERK signaling pathway. PI3K inhibitor LY294002 synergistically enhanced DRβ-H-induced apoptosis whereas MEK inhibitor U0126 reduced the apoptosis rate. Moreover, DRβ-H regulated the ratio of pro-apoptotic and anti-apoptotic Bcl-2 family proteins. Furthermore, DRβ-H induced depolarization of mitochondrial membrane potential which released Apaf-1 and Cytochrome C from the inter membrane space into the cytosol, where they promoted caspase-9 and caspase-3 activation. This is the first report on the pro-apoptotic effects of DRβ-H, a novel oleanane-type triterpenoid saponin, on breast cancer cells and its comprehensive apoptosis pathways. It implied that oleanane-type triterpenoid saponin DRβ-H could be a promising candidate for chemotherapy of breast cancer.
authors.affiliation: Jiangsu Breast Disease Center, the First Affiliated Hospital with Nanjing Medical University, Nanjing, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Cheng
authors.affiliation: Jiangsu Breast Disease Center, the First Affiliated Hospital with Nanjing Medical University, Nanjing, China.
authors.forename: Tian-Song
authors.initials: TS
authors.lastname: Xia
authors.affiliation: State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, China.
authors.forename: Yi-Fen
authors.initials: YF
authors.lastname: Wang
authors.affiliation: Jiangsu Breast Disease Center, the First Affiliated Hospital with Nanjing Medical University, Nanjing, China.
authors.forename: Wenbin
authors.initials: W
authors.lastname: Zhou
authors.affiliation: Jiangsu Breast Disease Center, the First Affiliated Hospital with Nanjing Medical University, Nanjing, China.
authors.forename: Xiu-Qing
authors.initials: XQ
authors.lastname: Liang
authors.affiliation: Jiangsu Breast Disease Center, the First Affiliated Hospital with Nanjing Medical University, Nanjing, China.
authors.forename: Jin-Qiu
authors.initials: JQ
authors.lastname: Xue
authors.affiliation: Jiangsu Breast Disease Center, the First Affiliated Hospital with Nanjing Medical University, Nanjing, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Shi
authors.affiliation: Jiangsu Breast Disease Center, the First Affiliated Hospital with Nanjing Medical University, Nanjing, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Jiangsu Breast Disease Center, the First Affiliated Hospital with Nanjing Medical University, Nanjing, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Ding
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053477:Apoptotic Protease-Activating Factor 1 / Q000378:metabolism; D001943:Breast Neoplasms; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D002867:Chromones / Q000494:pharmacology; D045304:Cytochromes c / Q000378:metabolism; D004354:Drug Screening Assays, Antitumor; D004357:Drug Synergism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D006801:Humans; D020935:MAP Kinase Signaling System; D061986:MCF-7 Cells; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D009025:Morpholines / Q000494:pharmacology; D009828:Oleanolic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D012503:Saponins / Q000494:pharmacology*
chemical_list: C506592:APAF1 protein, human; D000970:Antineoplastic Agents; D053477:Apoptotic Protease-Activating Factor 1; D002867:Chromones; C000595098:D rhamnose beta-hederin; D009025:Morpholines; D019253:Proto-Oncogene Proteins c-bcl-2; D012503:Saponins; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D009828:Oleanolic Acid; D045304:Cytochromes c; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; C505407:CASP3 protein, human; C506433:CASP9 protein, human; D053148:Caspase 3; D053453:Caspase 9