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Title: TNP-470, A Methionine Aminopeptidase-2 Inhibitor, Inhibits Cell Proliferation, Migration and Invasion of Human Cholangiocarcinoma Cells In Vitro
Authors: Sonexai, KIDOIKHAMMOUAN
Keywords: TNP-470 - MetAP - MetAP2 -
MMP9 - metastasis -
Issue Date: 13-Dec-2012
Publisher: Asian Pacific Journal of Cancer Prevention
Citation: Asian Pacific J Cancer Prev, 13, 155-160
Series/Report no.: Asian Pacific Journal of Cancer Prevention;13
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.
Description: and diminution of MetAP2 activity using fumagillin, a specific MetAP2 inhibitor, which effectively reduced cell proliferation of human CCA cell lines (Sawanyawisuth et al., 2007). In the present study, we determined the effect of TNP-470 on growth, migration and invasion of human CCA cell lines. The expression levels of c-MYC, MMP2 and MMP9 which are the key effectors of growth, migration and invasion processes (Sanceau et al., 2003; Prochownik 2004; Sun et al., 2008; Slack-Davis et al., 2009) were also explored.
ISSN: 155-160

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