The Apoptotic Effect of D Rhamnose β-Hederin, a Novel Oleanane-Type Triterpenoid Saponin on Breast Cancer Cells

• Published in: PloS one Vol. 9; no. 3; p. e90848
• Main Authors: Cheng, Lin, Xia, Tian-Song, Wang, Yi-Fen, Zhou, Wenbin, Liang, Xiu-Qing, Xue, Jin-Qiu, Shi, Liang, Wang, Ying, Ding, Qiang
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 06.03.2014; Public Library of Science (PLoS)
• Subjects: 1-Phosphatidylinositol 3-kinase; AKT protein; Anticancer properties; Antifungal agents; Antineoplastic Agents - pharmacology; Apaf-1 protein; Apoptosis; Apoptosis - drug effects; Apoptotic Protease-Activating Factor 1 - metabolism; Bcl-2 protein; Biology; Breast cancer; Breast Neoplasms; Cancer; Caspase; Caspase 3 - metabolism; Caspase 9 - metabolism; Caspase-3; Caspase-9; Chemopreventive agents; Chemotherapy; Chromones - pharmacology; Clematis ganpiniana; Cytochrome; Cytochrome c; Cytochromes c - metabolism; Cytosol; Cytotoxicity; Depolarization; Drug Screening Assays, Antitumor; Drug Synergism; Extracellular signal-regulated kinase; Extracellular Signal-Regulated MAP Kinases - metabolism; Female; Ginseng; Ginsenosides; Humans; Inhibitors; Kinases; MAP Kinase Signaling System; MCF-7 Cells; Medical research; Medicine; Membrane potential; Membrane Potential, Mitochondrial - drug effects; Metastasis; Mitochondria; Morpholines - pharmacology; Natural products; Oleanolic Acid - analogs & derivatives; Oleanolic Acid - pharmacology; Phosphatidylinositol 3-Kinases - metabolism; Proteins; Proto-Oncogene Proteins c-akt - metabolism; Proto-Oncogene Proteins c-bcl-2 - metabolism; Rhamnose; Saponins; Saponins - pharmacology; Signal transduction; Signaling; Studies; Triterpenoids
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0090848

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.