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.
Highlights
Breast cancer is a worldwide malignant disease and a major cause of death in women [1]
D Rhamnose b-hederin (DRb-H) markedly decreased phosphorylated AKT at late time point (48 h), we focused on the PI3K/AKT signaling to account for its inhibitory mechanism
We reported that DRb-H, a novel oleanane-type triterpenoid saponin, had strong inhibitory activity on different breast cancer cells
Summary
Breast cancer is a worldwide malignant disease and a major cause of death in women [1]. Many anti-cancer agents have shown efficacy in extending the survival of breast cancer patients. Disease-free survival and overall survival have been significantly improved, there are still some patients died of breast cancer after systemic therapies, especially for advanced breast cancer [2]. Using compounds from natural plants as potential cancer preventive and/or therapeutic agents has become a fascinating strategy [3,4]. Identification and investigation of active components from natural plants are important for assessing their potential for clinical use. A large number of components purified from herbs have been used to curing various cancers including breast cancer. Development of new therapeutic agents from natural source has great promise for breast cancer treatment
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