title: TNP-470, a methionine aminopeptidase-2 inhibitor, inhibits cell proliferation, migration and invasion of human cholangiocarcinoma cells in vitro.
abstract: Methionine aminopeptidase-2 (MetAP2) is over-expressed in several cancers, including the cholangiocarcinoma (CCA). We reported previously suppressive effects of fumagillin, a MetAP2 inhibitor, on growth of CCA cell lines. In the present study, we evaluated the anti-proliferative and anti-invasive activities of TNP-470, a fumagillin analogue with higher MetAP2 inhibitory activity, on CCA cell lines (KKU-M213 and KKU-M214). TNP-470 significantly inhibited growth of both lines in a dose and time dependent fashion. Moreover, a sub-toxic dose of TNP-470 significantly reduced migration and invasion of CCA cells. Exploration of the molecular mechanisms by which TNP-470 inhibited growth and metastasis of CCA cell lines demonstrated expression of c-MYC, MMP2 and MMP9 to be decreased in TNP-470 treated cells. These results suggest that TNP-470 could be a potential therapeutic agent for CCA.
authors.affiliation: Department of Biochemistry, Khon Kaen University, Khon Kaen, Thailand.
authors.forename: Sonexai
authors.initials: S
authors.lastname: Kidoikhammouan
authors.forename: Wunchana
authors.initials: W
authors.lastname: Seubwai
authors.forename: Nattawat
authors.initials: N
authors.lastname: Tantapotinan
authors.forename: Atit
authors.initials: A
authors.lastname: Silsirivanit
authors.forename: Sopit
authors.initials: S
authors.lastname: Wongkham
authors.forename: Kanlayanee
authors.initials: K
authors.lastname: Sawanyawisuth
authors.forename: Chaisiri
authors.initials: C
authors.lastname: Wongkham
mesh_terms: D000626:Aminopeptidases; D001650:Bile Duct Neoplasms; D001653:Bile Ducts, Intrahepatic; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D018281:Cholangiocarcinoma; D006801:Humans; D008715:Methionine
chemical_list: D008715:Methionine; D000626:Aminopeptidases