title: Isoflavones extracted from chickpea Cicer arietinum L. sprouts induce mitochondria-dependent apoptosis in human breast cancer cells.
abstract: Isoflavones are important chemical components of the seeds and sprouts of chickpeas. We systematically investigated the effects of isoflavones extracted from chickpea sprouts (ICS) on the human breast cancer cell lines SKBr3 and Michigan Cancer Foundation-7 (MCF-7). 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays showed that ICS (10-60 µg/mL) significantly inhibited the proliferation of both cell lines in a time-dependent and dose-dependent fashion. Wright-Giemsa staining as well as annexin V-fluorescein isothiocyanate and propidium iodide (Annexin V/PI) staining showed that ICS significantly increased cytoclasis and apoptotic body formation. Quantitative Annexin V/PI assays further showed that the number of apoptotic cells increased in a dose-dependent manner following ICS treatment. Semiquantitative reverse transcription PCR showed that ICS increased the expression of the apoptosis-promoting gene Bcl-2-associated X protein and decreased the expression of the antiapoptotic gene Bcl-2. Western blot analysis showed that treatment of SKBr3 and MCF-7 cells with ICS increased the expression of caspase 7, caspase 9, P53, and P21 in a dose-dependent manner. Flow cytometry assays using the fluorescent probe 3,3'-dihexyloxacarbocyanine iodide showed a dose-dependent decrease in mitochondrial membrane potential following ICS treatment. Treatment using ICS also induced a dose-dependent increase in reactive oxygen species production. This is the first study to demonstrate that ICS may be a chemopreventive or therapeutic agent against breast cancer.
authors.affiliation: State Key Laboratory Basis of Xinjiang Indigenous Medicinal Plants Resource Utilization, Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Urumqi, 830011, China; A Key Laboratory of Plant Resources and Chemistry of Arid Zone, Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Urumqi, 830011, China; University of Chinese Academy of Sciences, Beijing, 100049, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Chen
authors.forename: Hai-Rong
authors.initials: HR
authors.lastname: Ma
authors.forename: Yan-Hua
authors.initials: YH
authors.lastname: Gao
authors.forename: Xue
authors.initials: X
authors.lastname: Zhang
authors.forename: Madina
authors.initials: M
authors.lastname: Habasi
authors.forename: Rui
authors.initials: R
authors.lastname: Hu
authors.forename: Haji Akber
authors.initials: HA
authors.lastname: Aisa
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000378:metabolism*; D053179:Caspase 7 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D029863:Cicer / Q000737:chemistry*; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D005260:Female; D006801:Humans; D007529:Isoflavones / Q000494:pharmacology*; D061986:MCF-7 Cells; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: C494826:BAX protein, human; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D007529:Isoflavones; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; C505520:CASP7 protein, human; C506433:CASP9 protein, human; D053179:Caspase 7; D053453:Caspase 9
keywords: Cicer arietinum L. sprouts; breast cancer cells; isoflavones; mitochondria-dependent apoptosis