title: Codonolactone, a sesquiterpene lactone isolated from Chloranthus henryi Hemsl, inhibits breast cancer cell invasion, migration and metastasis by downregulating the transcriptional activity of Runx2.
abstract: Metastasis is the most insidious aspect of breast cancer, but effective strategies to control this malignant process are still lacking. In previous studies, we screened over 200 extracts from plants of genus Chloranthaceae by bioactivity-guided fractionation, and found that Codonolactone (CLT) exhibited potential antimetastatic properties in breast cancer cells. This sesquiterpene lactone was isolated from Chloranthus henryi Hemsl, and is also found in other medical herbs, such as Codonopsis pilosula, Atractylodes macrocephala Koidz and others. Here, we report that CLT inhibited the ability of invasion and migration in metastatic breast cancer cells. Furthermore, CLT exhibited significant suppression on formation of lung metastatic foci of breast cancer in vivo. We next investigated the mechanism of CLT-induced metastasis inhibitory effects in breast cancer cells. A significant inhibition on activity and expression of MMP-9 and MMP-13 was observed. Moreover, data from western blotting, Runx2 transcription factor assay and chromatin immunoprecipitation assay showed that binding ability of Runx2 to sequences of the mmp-13 promoter was inhibited by CLT. Collectively, these findings suggested that the antimetastatic properties of CLT in breast cancer were due to the inhibition of MMPs, which might be associated with a downregulation of Runx2 transcriptional activity.
authors.affiliation: Department of Pharmacology, School of Pharmacy, Jiangxi University of Traditional Chinese Medicine, Nanchang 330004, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, School of Pharmacy, Jiangxi University of Traditional Chinese Medicine, Nanchang 330004, P.R. China.
authors.forename: Bin
authors.initials: B
authors.lastname: Chen
authors.affiliation: Hospital of Nanchang University, Nanchang 330047, P.R. China.
authors.forename: Ruolan
authors.initials: R
authors.lastname: Zou
authors.affiliation: Department of Pharmacology, School of Pharmacy, Jiangxi University of Traditional Chinese Medicine, Nanchang 330004, P.R. China.
authors.forename: Xiuying
authors.initials: X
authors.lastname: Tu
authors.affiliation: Department of Pharmacology, School of Pharmacy, Jiangxi University of Traditional Chinese Medicine, Nanchang 330004, P.R. China.
authors.forename: Songlin
authors.initials: S
authors.lastname: Tan
authors.affiliation: Network and Educational Technology Center, Jiangxi University of Traditional Chinese Medicine, Nanchang 330004, P.R. China.
authors.forename: Hong
authors.initials: H
authors.lastname: Lu
authors.affiliation: Department of Pharmacology, School of Pharmacy, Jiangxi University of Traditional Chinese Medicine, Nanchang 330004, P.R. China.
authors.forename: Zhaojie
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Pharmacology, School of Pharmacy, Jiangxi University of Traditional Chinese Medicine, Nanchang 330004, P.R. China.
authors.forename: Jianjiang
authors.initials: J
authors.lastname: Fu
mesh_terms: D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D045744:Cell Line, Tumor; D050659:Core Binding Factor Alpha 1 Subunit / Q000096:biosynthesis*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007783:Lactones / Q000008:administration & dosage* / Q000737:chemistry; D010936:Plant Extracts / Q000008:administration & dosage / Q000737:chemistry; D012717:Sesquiterpenes / Q000008:administration & dosage* / Q000737:chemistry; D015533:Transcriptional Activation / Q000187:drug effects; D057948:Viridiplantae / Q000737:chemistry
chemical_list: D050659:Core Binding Factor Alpha 1 Subunit; D007783:Lactones; D010936:Plant Extracts; C493709:RUNX2 protein, human; D012717:Sesquiterpenes