PloS one, 2014-03, Vol.9 (6), p.e90848
2014
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- Autor(en) / Beteiligte
- Titel
- The apoptotic effect of D Rhamnose β-hederin, a novel oleanane-type triterpenoid saponin on breast cancer cells
- Ist Teil von
- PloS one, 2014-03, Vol.9 (6), p.e90848
- Ort / Verlag
- United States: Public Library of Science
- Erscheinungsjahr
- 2014
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1932-6203eISSN: 1932-6203DOI: 10.1371/journal.pone.0090848Titel-ID: cdi_plos_journals_1504772401
- Format
- –
- Schlagworte
- 1-Phosphatidylinositol 3-kinase, AKT protein, Anticancer properties, 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