title: Butein Shows Cytotoxic Effects and Induces Apoptosis in Human Ovarian Cancer Cells.
abstract: Butein is a polyphenol, one of the compounds of chalcones, which are flavonoids that are widely biosynthesized in plants, and exhibits different pharmacological activities. Plants containing butein have been used in Chinese traditional medicine. Recently, it has been reported that butein suppresses proliferation and triggers apoptosis in various human cancer cells in vitro and in vivo. The aim of this study was to investigate its pro-apoptotic effect and mechanisms in two cultured human ovarian cancer cells (ES-2 and TOV-21G). The effects of butein on cell viability were assessed by a MTT assay at 3, 10, 30, and 100 μ/M. The apoptotic pathway related factors, including the mitochondrial transmembrane potential (MTP), cytochrome c, caspase cascade, and Bcl-2 family proteins, were examined. MTT assay revealed that butein was cytotoxic to both ovarian cancer cells in a dose- and time-dependent manner. JC-1 flow cytometry, cytochrome c, and caspase activity assays revealed that butein damaged the MTP, increased the level of cytosol cytochrome c and the activities of caspase-3, -8, and -9 in the two ovarian cancer cells. Western blot analysis revealed that butein down-regulated the anti-apoptotic proteins Bcl-2 and Bcl-xL and increased the pro-apoptotic proteins Bax and Bad. These findings suggest that butein-induced apoptosis in ovarian cancer cells via the activation of both extrinsic and intrinsic pathways. In addition, butein also down-regulated the expressions of the inhibitor of apoptosis (IAP) proteins, XIAP, survivin, CIAP-1, and CIAP-2. This indicates that the inhibition of IAP proteins was also involved in butein-induced apoptosis. The results of our study suggest that butein may be a promising anticancer agent in treating ovarian cancer.
authors.affiliation: Department of Medical Research, Show Chwan Memorial Hospital, Changhua 500, Taiwan, ROC.
authors.forename: Pei-Yu
authors.initials: PY
authors.lastname: Yang
authors.affiliation: Tissue Culture Center, New York Eye & Ear Infirmary of Mount Sinai, New York, NY, USA.
authors.forename: Dan-Ning
authors.initials: DN
authors.lastname: Hu
authors.affiliation: Department of Family Medicine, Changhua Christian Hospital, Changhua, Taiwan, ROC.|Faculty of Medicine, Chung Shan Medical University, Taichung, Taiwan, ROC.
authors.forename: I-Ching
authors.initials: IC
authors.lastname: Lin
authors.affiliation: Cancer Center, Show Chwan Memorial Hospital, Changhua 500, Taiwan, ROC.
authors.forename: Fu-Shing
authors.initials: FS
authors.lastname: Liu
mesh_terms: D000972:Antineoplastic Agents, Phytogenic; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D000075747:Baculoviral IAP Repeat-Containing 3 Protein; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D047188:Chalcones / Q000494:pharmacology* / Q000627:therapeutic use; D045304:Cytochromes c / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D058990:Molecular Targeted Therapy; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D008517:Phytotherapy; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D000077022:Survivin; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000378:metabolism; D051020:bcl-X Protein / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; C494811:BCL2L1 protein, human; C107489:BIRC5 protein, human; D047188:Chalcones; D051034:Inhibitor of Apoptosis Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D000077022:Survivin; D051636:X-Linked Inhibitor of Apoptosis Protein; C496866:XIAP protein, human; D051020:bcl-X Protein; C040918:butein; D045304:Cytochromes c; C494832:BIRC3 protein, human; D000075747:Baculoviral IAP Repeat-Containing 3 Protein; D044767:Ubiquitin-Protein Ligases; D020169:Caspases
keywords: Apoptosis; Butein; Inhibitor of Apoptosis; Ovarian Cancer