title: Sanguinarine inhibits vascular endothelial growth factor release by generation of reactive oxygen species in MCF-7 human mammary adenocarcinoma cells.
abstract: The inhibitory action and the possible mechanism of anticancer compound Sanguinarine (SAN) on vascular endothelial growth factor (VEGF) in human mammary adenocarcinoma cells MCF-7 were evaluated in this study. We exposed MCF-7 to SAN for 24 h, then cell viability was assessed by using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction assay. Human VEGF was measured using a paired antibody quantitative ELISA kit, relative expression of VEGF mRNA was calculated using the real-time PCR studies, and the effect of SAN on the reactive oxygen species (ROS) level was detected by the flow cytometer. Treatment with SAN remarkably inhibited growth of MCF-7 cells and induced cell apoptosis. We found that VEGF release was stimulated by subtoxic concentrations of SAN and inhibited by high dose of SAN, SAN-evoked VEGF release was mimicked by low concentration of H2O2, and SAN-regulated VEGF inhibition was accompanied by increasing of ROS; these changes were abolished by antioxidant. High concentration of SAN inhibited VEGF mRNA expression in MCF-7 cultures, suggesting an effect at transcriptional level, and was also abolished by antioxidant. The present findings indicated that the regulation of VEGF expression and release from MCF-7 cells were possibly through reactive oxygen species evoked by SAN.
authors.affiliation: Department of Clinical Pharmacology, Chinese PLA General Hospital, Beijing 100853, China.
authors.forename: Xian-zhe
authors.initials: XZ
authors.lastname: Dong
authors.forename: Miao
authors.initials: M
authors.lastname: Zhang
authors.forename: Kun
authors.initials: K
authors.lastname: Wang
authors.forename: Ping
authors.initials: P
authors.lastname: Liu
authors.forename: Dai-hong
authors.initials: DH
authors.lastname: Guo
authors.forename: Xiao-li
authors.initials: XL
authors.lastname: Zheng
authors.forename: Xiao-yue
authors.initials: XY
authors.lastname: Ge
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D053119:Benzophenanthridines / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D005260:Female; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007546:Isoquinolines / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D061986:MCF-7 Cells; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*
chemical_list: D053119:Benzophenanthridines; D007546:Isoquinolines; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C005705:sanguinarine; D013482:Superoxide Dismutase; D000111:Acetylcysteine