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Open Access 01-12-2009 | Short communication

NC2213: a novel methionine aminopeptidase 2 inhibitor in human colon cancer HT29 cells

Authors: Ponniah Selvakumar, Ashakumary Lakshmikuttyamma, Umashankar Das, Hari N Pati, Jonathan R Dimmock, Rajendra K Sharma

Published in: Molecular Cancer | Issue 1/2009

Abstract

Methionine aminopeptidase 2 (MetAP2) is a bifunctional protein that plays a critical role in the regulation of post-translational processing and protein synthesis. MetAP2 is overexpressed in human colon cancer. In this report we screened various MetAP2 inhibitors and treated HT29 cells with various concentrations of compounds. We evaluated the expression of MetAP2 and pp60^c-src expressions in HT29 cells. In addition we also carried out the cell proliferation and cell cycle analysis in the MetAP2 inhibitor-treated HT29 cells. The cell cycle analysis of HT29 treated with 1.0 μM of NC2213 showed an arrest in the G2 phase followed by an induction in the percentage of cells undergoing apoptosis in the sub-G1 phase. Western blot analysis revealed that the MetAP2 expression was dose-dependently decreased when the HT29 cells were treated with the 3,5-bis(benzylidene)-4-piperidone derivative (NC2213). In addition, phosphorylation of Src, a myristoylated oncoprotein was significantly decreased by 1.0 μM of NC2213 as revealed by Western blot analysis. Furthermore, NC2213 also inhibits the expression of pp60^c-src in HT29 cells. Interestingly, this compound also inhibits the phosphorylation at Tyr416 of pp60^c-src while increasing the phosphorylation at Tyr527 of pp60^c-src. NC2213 inhibits the growth of HT29 cells by inducing apoptosis and might be useful for the treatment of human colon cancer.

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Title: NC2213: a novel methionine aminopeptidase 2 inhibitor in human colon cancer HT29 cells
Authors: Ponniah Selvakumar
Ashakumary Lakshmikuttyamma
Umashankar Das
Hari N Pati
Jonathan R Dimmock
Rajendra K Sharma
Publication date: 01-12-2009
Publisher: BioMed Central
Published in: Molecular Cancer / Issue 1/2009
Electronic ISSN: 1476-4598
DOI: https://doi.org/10.1186/1476-4598-8-65

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