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: Sonexai Kidoikhammouan, Wunchana Seubwai, Nattawat Tantapotinan, Atit Silsirivanit, Sopit Wongkham, Kanlayanee Sawanyawisuth, Chaisiri Wongkham
• Journal: Asian Pacific journal of cancer prevention : APJCP (Asian Pac J Cancer Prev) Vol. 13 Suppl Pg. 155-60 ( 2012) ISSN: 2476-762X [Electronic] Thailand
• PMID: 23480758 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Methionine
• Aminopeptidases

Topics

• Aminopeptidases
• Bile Duct Neoplasms
• Bile Ducts, Intrahepatic
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Cholangiocarcinoma
• Humans
• Methionine