title: 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.affiliation: Engineering Research Center of Forest Bio-Preparation, Ministry of Education, Northeast Forestry University, Harbin 150040, PR China.
authors.forename: Wei-Dong
authors.initials: WD
authors.lastname: Ma
authors.affiliation: The 2nd Affiliated Hospital of Harbin Medical University, Harbin 150001, PR China.
authors.forename: Yong-Peng
authors.initials: YP
authors.lastname: Zou
authors.affiliation: Engineering Research Center of Forest Bio-Preparation, Ministry of Education, Northeast Forestry University, Harbin 150040, PR China.
authors.forename: Peng
authors.initials: P
authors.lastname: Wang
authors.affiliation: Engineering Research Center of Forest Bio-Preparation, Ministry of Education, Northeast Forestry University, Harbin 150040, PR China.
authors.forename: Xiao-Hui
authors.initials: XH
authors.lastname: Yao
authors.affiliation: Engineering Research Center of Forest Bio-Preparation, Ministry of Education, Northeast Forestry University, Harbin 150040, PR China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Engineering Research Center of Forest Bio-Preparation, Ministry of Education, Northeast Forestry University, Harbin 150040, PR China.
authors.forename: Ming-Hui
authors.initials: MH
authors.lastname: Duan
authors.affiliation: Engineering Research Center of Forest Bio-Preparation, Ministry of Education, Northeast Forestry University, Harbin 150040, PR China. Electronic address: yujie_fu@163.com.
authors.forename: Yu-Jie
authors.initials: YJ
authors.lastname: Fu
authors.affiliation: The 2nd Affiliated Hospital of Harbin Medical University, Harbin 150001, PR China. Electronic address: yubodr@163.com.
authors.forename: Bo
authors.initials: B
authors.lastname: Yu
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D017304:Annexin A5 / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D053453:Caspase 9 / Q000235:genetics / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D053938:DNA Fragmentation / Q000187:drug effects; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives / Q000378:metabolism; D006801:Humans; D020128:Inhibitory Concentration 50; D061986:MCF-7 Cells; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D009285:Naphthoquinones / Q000494:pharmacology*; D029598:Passiflora / Q000737:chemistry; D011419:Propidium / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism; D051025:bcl-Associated Death Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D017304:Annexin A5; C494819:BAD protein, human; C494826:BAX protein, human; C492760:FITC-annexin A5; D009285:Naphthoquinones; D017382:Reactive Oxygen Species; D051028:bcl-2-Associated X Protein; D051025:bcl-Associated Death Protein; D011419:Propidium; C505407:CASP3 protein, human; C506433:CASP9 protein, human; D053148:Caspase 3; D053453:Caspase 9; D016650:Fluorescein-5-isothiocyanate; C057774:chimaphilin; D000111:Acetylcysteine
keywords: Apoptosis; Chimaphilin; MCF-7; Mitochondrial; Reactive oxygen species