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.
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.