title: Procyanidin C1 from Cinnamomi Cortex inhibits TGF-β-induced epithelial-to-mesenchymal transition in the A549 lung cancer cell line.
abstract: Cancer metastasis is one of the most critical events in cancer patients, and the median overall survival of stage IIIb or IV patients with metastatic lung cancer in the TNM classification is only 8 or 5 months, respectively. We previously demonstrated that Juzentaihoto, a Japanese traditional medicine, can inhibit cancer metastasis through the activation of macrophages and T cells in mouse cancer metastatic models; however, the mechanism(s) through which Juzentaihoto directly affects tumor cells during the metastasis process and which herbal components from Juzentaihoto inhibit the metastatic potential have not been elucidated. In this study, we focused on the epithelial-to-mesenchymal transition (EMT), which plays an important role in the formation of cancer metastasis. We newly determined that only the Cinnamomi Cortex (CC) extract, one of 10 herbal components of Juzentaihoto, inhibits TGF-β-induced EMT. Moreover, the contents of catechin trimer in CC extracts were significantly correlated with the efficacy of inhibiting TGF-β-induced EMT. Finally, the structure of the catechin trimer from CC extract was chemically identified as procyanidin C1 and the compound showed inhibitory activity against TGF-β-induced EMT. This illustrates that procyanidin C1 is the main active compound in the CC extract responsible for EMT inhibition and that procyanidin C1 could be useful as a lead compound to develop inhibitors of cancer metastasis and other diseases related to EMT.
authors.affiliation: Division of Pathogenic Biochemistry, Institute of Natural Medicine, University of Toyama, Toyama 930-0194, Japan.
authors.forename: Ryoei
authors.initials: R
authors.lastname: Kin
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Kato
authors.forename: Naoki
authors.initials: N
authors.lastname: Kaneto
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Sakurai
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Hayakawa
authors.forename: Feng
authors.initials: F
authors.lastname: Li
authors.forename: Ken
authors.initials: K
authors.lastname: Tanaka
authors.forename: Ikuo
authors.initials: I
authors.lastname: Saiki
authors.forename: Satoru
authors.initials: S
authors.lastname: Yokoyama
mesh_terms: D044946:Biflavonoids / Q000494:pharmacology*; D015820:Cadherins / Q000378:metabolism; D002392:Catechin / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002935:Cinnamomum zeylanicum; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D009362:Neoplasm Metastasis / Q000188:drug therapy / Q000473:pathology; D010936:Plant Extracts / Q000494:pharmacology; D044945:Proanthocyanidins / Q000494:pharmacology*; D051899:Smad2 Protein / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism*
chemical_list: D044946:Biflavonoids; D015820:Cadherins; D004365:Drugs, Chinese Herbal; D010936:Plant Extracts; D044945:Proanthocyanidins; C497782:SMAD2 protein, human; D051899:Smad2 Protein; D016212:Transforming Growth Factor beta; C532132:cinnamomi cortex; C479583:procyanidin C; D002392:Catechin