title: Halofuginone induces the apoptosis of breast cancer cells and inhibits migration via downregulation of matrix metalloproteinase-9.
abstract: Halofuginone (HF) is extracted from Dichroa febrifuga, a plant used in traditional medicine. We report that the HF extract inhibits the growth of breast cancer cells and induces the generation of reactive oxygen species (ROS) and apoptosis, an important feature of potential anticancer agents. In addition, HF significantly reduces the migration and invasion of MCF-7 and MDA-MB-231 human breast cancer cells after 12-O-tetraecanoylphorbol-13-acetate (TPA) stimulation. As matrix metalloproteinase-9 plays a critical role in tumor metastasis, we analyzed its expression with the HF extract treatment. Western blot analysis and gelatin zymography showed that HF suppresses MMP-9 expression and activity concentration-dependently. HF also decreases the nuclear protein levels of nuclear factor kappa B (NF-κB) and c-fos (AP-1), critical transcription factors regulating MMP-9 expression through binding the MMP-9 promoter region. Luciferase assays showed that HF decreases TPA-induced MMP-9 promoter binding activities of NF-κB and AP-1. Taken together, these are the first results indicating that halofuginone may represent a promising new agent for breast cancer chemotherapy.
authors.affiliation: Department of Microbiology, Pusan National University, Busan 609-735, Republic of Korea.
authors.forename: Mei Ling
authors.initials: ML
authors.lastname: Jin
authors.forename: Sun Young
authors.initials: SY
authors.lastname: Park
authors.forename: Young Hun
authors.initials: YH
authors.lastname: Kim
authors.forename: Geuntae
authors.initials: G
authors.lastname: Park
authors.forename: Sang Joon
authors.initials: SJ
authors.lastname: Lee
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D061986:MCF-7 Cells; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis* / Q000235:genetics; D016328:NF-kappa B / Q000096:biosynthesis; D010880:Piperidines / Q000008:administration & dosage*; D051057:Proto-Oncogene Proteins c-akt / Q000096:biosynthesis; D052999:Quinazolinones / Q000008:administration & dosage*; D018808:Transcription Factor AP-1 / Q000235:genetics
chemical_list: D016328:NF-kappa B; D010880:Piperidines; D052999:Quinazolinones; D018808:Transcription Factor AP-1; D051057:Proto-Oncogene Proteins c-akt; D020780:Matrix Metalloproteinase 9; C010176:halofuginone