Cycloartane triterpenoids from Cimicifuga yunnanensis induce apoptosis of breast cancer cells (MCF7) via p53-dependent mitochondrial signaling pathway.

Abstract

The present study was carried out to investigate the antitumor activity of five cycloartane triterpenoids isolated from Cimicifuga yunnanensis on the breast cancer cell line MCF7 and its corresponding drug resistant subline R-MCF7, including cimigenol-3-O-β-D-xylopyranoside (compound 1), 25-O-acetylcimigenol-3-O-β-D-xylopyranoside (compound 2), 25-chlorodeoxycimigenol-3-O-β-D-xylopyranoside (compound 3), 25-O-acetylcimigenol-3-O-α-L-arabinopyranoside (compound 4) and 23-O-acetylcimigenol-3-O-β-D-xylopyranoside (compound 5). The results showed that compounds 2-5 have relatively high antitumor activity on both MCF7 and R-MCF7 cells. The involvement of apoptosis as a major cause of cycloartane triterpenoids-induced cell death was further confirmed. The results of RT-PCR showed that compounds 2-5 increased the expression of p53 and bax, which led to the loss of mitochondrial potential and then resulted in the activation of caspase-7. These findings collectively demonstrated that compounds 2-5 induced apoptosis of MCF7 via p53-dependent mitochondrial pathway.

• Authors: Zhong-Ze Fang, Yin Nian, Wei Li, Jing-Jing Wu, Guang-Bo Ge, Pei-Pei Dong, Yan-Yan Zhang, Ming-Hua Qiu, Lei Liu, Ling Yang
• Journal: Phytotherapy research : PTR (Phytother Res) Vol. 25 Issue 1 Pg. 17-24 (Jan 2011) ISSN: 1099-1573 [Electronic] England
• PMID: 20564500 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2010 John Wiley & Sons, Ltd.

Chemical References

• Antineoplastic Agents, Phytogenic
• Triterpenes
• Tumor Suppressor Protein p53
• cycloartane
• Caspase 7

Topics

• Antineoplastic Agents, Phytogenic (chemistry, pharmacology, therapeutic use)
• Apoptosis (drug effects)
• Breast Neoplasms (drug therapy)
• Caspase 7 (metabolism)
• Cimicifuga (chemistry)
• Drug Resistance, Neoplasm
• Enzyme Activation (drug effects)
• Female
• Humans
• Membrane Potential, Mitochondrial (drug effects)
• Mitochondria (drug effects)
• Phytotherapy
• Reverse Transcriptase Polymerase Chain Reaction
• Signal Transduction (drug effects)
• Triterpenes (chemistry, pharmacology, therapeutic use)
• Tumor Cells, Cultured
• Tumor Suppressor Protein p53 (metabolism)
• Up-Regulation