title: Novel suppressive effects of cardamonin on the activity and expression of transglutaminase-2 lead to blocking the migration and invasion of cancer cells.
abstract: OBJECTIVE
  Alpinia katsumadai was recently found in our previous study to have anti-migratory and anti-invasion activities against HT-1080 cells. However, the study did not demonstrate the exact component of Alpinia katsumadai with anti-migratory and anti-invasive activities. We tested the effects and relevant mechanism of cardamonin (CDN) on the migration and invasion of cancer cells.
  
  
  METHODS
  Migration and invasion of cancer cells were measured using multi-well chambers. Zymography and Western blots were used to examine the effects of CDN on the activities of matrix metalloproteinases (MMPs) and expression of transglutaminase-2 (Tgase-2).
  
  
  RESULTS
  CDN, but not alpinetin, dose-dependently suppressed the migration and 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced invasion of HT-1080 sarcoma cells. CDN suppressed the expression of Tgase-2, MMP-2, NF-κB and MMP-9 in HT-1080 cells, and suppressed MMP-2 and MMP-9 activities. Gene silencing of Tgase-2 suppressed the migration and invasion of HT-1080 cells and suppressed the activities of MMP-2 and MMP-9. Migration of various cancer cells having high levels of Tgase-2 were also inhibited by CDN. CDN and Alpinia katsumadai extracts also directly inhibited the activity of Tgase-2.
  
  
  CONCLUSIONS
  CDN inhibits migration of several cancer cell lines expressing Tgase-2 via suppression of Tgase-2 expression and inhibition of Tgase-2 activity. The finding that CDN has Tgase-2 inhibitory activity will give us a new scaffold or clue of pharmacophore for the development of more effective Tgase-2 inhibitors.
authors.affiliation: College of Pharmacy, Dongguk University, Seoul 100-715, Republic of Korea.
authors.forename: Mi Kyung
authors.initials: MK
authors.lastname: Park
authors.forename: Seung Ho
authors.initials: SH
authors.lastname: Jo
authors.forename: Hye Ja
authors.initials: HJ
authors.lastname: Lee
authors.forename: June Hee
authors.initials: JH
authors.lastname: Kang
authors.forename: You Ri
authors.initials: YR
authors.lastname: Kim
authors.forename: Hyun Ji
authors.initials: HJ
authors.lastname: Kim
authors.forename: Eun Ji
authors.initials: EJ
authors.lastname: Lee
authors.forename: Jae Young
authors.initials: JY
authors.lastname: Koh
authors.forename: Kyung Ok
authors.initials: KO
authors.lastname: Ahn
authors.forename: Kyung Chae
authors.initials: KC
authors.lastname: Jung
authors.forename: Seung Hyun
authors.initials: SH
authors.lastname: Oh
authors.forename: Soo Youl
authors.initials: SY
authors.lastname: Kim
authors.forename: Chang Hoon
authors.initials: CH
authors.lastname: Lee
mesh_terms: D045744:Cell Line, Tumor; D054443:Cell Migration Assays; D002465:Cell Movement / Q000187:drug effects* / Q000502:physiology; D047188:Chalcones / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D019204:GTP-Binding Proteins / Q000096:biosynthesis / Q000187:drug effects* / Q000502:physiology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000502:physiology; D020868:Gene Silencing / Q000187:drug effects / Q000502:physiology; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis / Q000187:drug effects / Q000502:physiology; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis / Q000187:drug effects / Q000502:physiology; D016328:NF-kappa B / Q000096:biosynthesis / Q000187:drug effects / Q000502:physiology; D009361:Neoplasm Invasiveness / Q000503:physiopathology* / Q000517:prevention & control; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases / Q000096:biosynthesis / Q000187:drug effects* / Q000502:physiology
chemical_list: D047188:Chalcones; D016328:NF-kappa B; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D019204:GTP-Binding Proteins; C436747:cardamonin