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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.
- Source :
- Chinese Medicine; 1/11/2016, Vol. 11, p1-11, 11p
- Publication Year :
- 2016
-
Abstract
- Background: Cycloartane triterpenoids exhibited anticancer efects. 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 identiied by IR, MS and NMR. Their anticancer efects 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 proile and annexin V staining were evaluated by low 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-β-D-(2-acetyl)xylopyranoside (ADHC-AXpn), together with the known 7,8-didehydrocimigenol-3-O-β-d-xylopyranoside (DHC-Xpn) were isolated. MCF-7 growth was signiicantly inhibited by ADHC-AXpn in a dose- and time-dependent manner (IC<subscript>50</subscript> : 27.81 µM at 48 h; P = 0.004 vs. control at 25 µM 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 IC<subscript>50</subscript> values for normal cells MCF10A (IC<subscript>50</subscript> : 78.63 µM at 48 h) than for tumor cells. In MCF-7 cells, ADHC-AXpn induced G<subscript>2</subscript>/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 efect might be associated with Raf/MEK/ERK signaling and Akt activation. Conclusions: ADHC-AXpn signiicantly suppressed the growth of MCF-7 cells, induced mitochondrial apoptosis and cell-cycle arrest, and inhibited Raf/MEK/ERK signaling pathway and Akt phosphorylation. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 17498546
- Volume :
- 11
- Database :
- Complementary Index
- Journal :
- Chinese Medicine
- Publication Type :
- Academic Journal
- Accession number :
- 112238120
- Full Text :
- https://doi.org/10.1186/s13020-015-0073-6