Please use this identifier to cite or link to this item: http://hdl.handle.net/10397/62419
Title: Novel cycloartane triterpenoid from cimicifuga foetida (Sheng Ma) induces mitochondrial apoptosis via inhibiting RAF/MEK/ERK pathway and AKT phosphorylation in human breast carcinoma MCF-7 cells
Authors: Sun, HY
Liu, BB
Hu, JY
Xu, LJ
Chan, SW
Chan, CO
Mok, DKW 
Zhang, DM
Ye, WC
Chen, SB
Issue Date: 2016
Publisher: BioMed Central
Source: Chinese medicine, 2016, v. 11, 1 How to cite?
Journal: Chinese medicine 
Abstract: Background: Cycloartane triterpenoids exhibited anticancer effects. This study aims to identify any potential novel anticancer cycloartane triterpenoids from Cimicifuga foetida L. rhizome (Sheng ma) and the mode of actions.
Methods: Cycloartane triterpenoids were isolated from the C. foetida rhizome by a series of column chromatography and identified by IR, MS and NMR. Their anticancer effects on several human cancer cell lines, MCF-7, HepG2, HepG2/ADM, HeLa, and PC3, and normal human mammary epithelial cells MCF10A were investigated by colony formation and MTT assays. Morphological analysis of apoptosis induction was performed by acridine orange/ethidium bromide dual-staining and Hoechst 33258 nuclear staining. The cell-cycle profile and annexin V staining were evaluated by flow cytometry. Apoptosis were investigated by measuring changes in mitochondrial membrane potential and analyzing expression of cell cycle-and apoptosis-related proteins in MCF-7 cells by Western blotting.
Results: A novel cycloartane triterpenoid, 25-O-acetyl-7,8-didehydrocimigenol-3-O-beta-d-(2-acetyl) xylopyranoside (ADHC-AXpn), together with the known 7,8-didehydrocimigenol-3-O-beta-d-xylopyranoside (DHC-Xpn) were isolated. MCF-7 growth was significantly inhibited by ADHC-AXpn in a dose-and time-dependent manner (IC50: 27.81 mu M at 48 h; P = 0.004 vs. control at 25 mu M for 48 h treatment), and ADHC-AXpn was selectively cytotoxic for cancerous cells (MCF-7, HepG2/ADM, HepG2 and HELA cells) based on its higher IC50 values for normal cells MCF10A (IC50: 78.63 mu M at 48 h) than for tumor cells. In MCF-7 cells, ADHC-AXpn induced G2/M cell cycle arrest by mediating cyclin-B1, and CDK1 and its phosphorylation; and induced apoptosis through the mitochondrial-mediated apoptotic pathway, with inhibition of Akt activation. As ADHC-AXpn suppressed phosphorylation of ERK1/2, Raf and Akt proteins in MCF-7 cells, its apoptotic effect might be associated with Raf/MEK/ERK signaling and Akt activation.
Conclusions: ADHC-AXpn significantly suppressed the growth of MCF-7 cells, induced mitochondrial apoptosis and cell-cycle arrest, and inhibited Raf/MEK/ERK signaling pathway and Akt phosphorylation.
URI: http://hdl.handle.net/10397/62419
ISSN: 1749-8546 (online)
DOI: 10.1186/s13020-015-0073-6
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