Chimaphilin induces apoptosis in human breast cancer MCF-7 cells through a ROS-mediated mitochondrial pathway.

Abstract

Chimaphilin, 2,7-dimethyl-1,4-naphthoquinone, is extracted from pyrola [Passiflora incarnata Fisch.]. In this study, the anticancer activity and underlying mechanisms of chimaphilin toward human breast cancer MCF-7 cells are firstly investigated. Chimaphilin could inhibit the viability of MCF-7 cells in a concentration-dependent manner, and the IC50 value was 43.30μM for 24h. Chimaphilin markedly induced apoptosis through the investigation of characteristic apoptotic morphological changes, nuclear DNA fragmentation, annexin V-FITC/propidium iodide (PI) double staining. Flow cytometry assay revealed that chimaphilin triggered a significant generation of ROS and disruption of mitochondrial membrane potential. Additionally, western blotting assay showed that chimaphilin suppressed Bcl-2 level and enhanced Bad level, then activated caspase-9 and caspase-3, and further activated the poly ADP-ribose polymerase (PARP), finally induced cell apoptosis involving the mitochondrial pathway. Furthermore, free radical scavengers N-acetyl-L-cysteine (NAC) pretreatment test testified that chimaphilin could increase the generation of ROS, then induce cell apoptosis. In general, the present results demonstrated that chimaphilin induced apoptosis in human breast cancer MCF-7 cells via a ROS-mediated mitochondrial pathway.

• Authors: Wei-Dong Ma, Yong-Peng Zou, Peng Wang, Xiao-Hui Yao, Yao Sun, Ming-Hui Duan, Yu-Jie Fu, Bo Yu
• Journal: Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association (Food Chem Toxicol) Vol. 70 Pg. 1-8 (Aug 2014) ISSN: 1873-6351 [Electronic] England
• PMID: 24793375 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Ltd. All rights reserved.

Chemical References

• Annexin A5
• BAD protein, human
• BAX protein, human
• FITC-annexin A5
• Naphthoquinones
• Reactive Oxygen Species
• bcl-2-Associated X Protein
• bcl-Associated Death Protein
• Propidium
• CASP3 protein, human
• CASP9 protein, human
• Caspase 3
• Caspase 9
• Fluorescein-5-isothiocyanate
• chimaphilin
• Acetylcysteine

Topics

• Acetylcysteine (pharmacology)
• Annexin A5 (metabolism)
• Apoptosis (drug effects)
• Caspase 3 (genetics, metabolism)
• Caspase 9 (genetics, metabolism)
• Cell Proliferation (drug effects)
• DNA Fragmentation (drug effects)
• Fluorescein-5-isothiocyanate (analogs & derivatives, metabolism)
• Humans
• Inhibitory Concentration 50
• MCF-7 Cells
• Membrane Potential, Mitochondrial (drug effects)
• Mitochondria (drug effects, metabolism)
• Naphthoquinones (pharmacology)
• Passiflora (chemistry)
• Propidium (metabolism)
• Reactive Oxygen Species (metabolism)
• bcl-2-Associated X Protein (genetics, metabolism)
• bcl-Associated Death Protein (genetics, metabolism)