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 fumagillinanalogue with higher MetAP2 inhibitory activity, on CCA cell lines (KKU-M213 and KKU-M214). TNP-470significantly inhibited growth of both lines in a dose and time dependent fashion. Moreover, a sub-toxic dose ofTNP-470 significantly reduced migration and invasion of CCA cells. Exploration of the molecular mechanismsby which TNP-470 inhibited growth and metastasis of CCA cell lines demonstrated expression of c-MYC, MMP2and MMP9 to be decreased in TNP-470 treated cells. These results suggest that TNP-470 could be a potentialtherapeutic agent for CCA.