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Investigational New Drugs
Published in: Investigational New Drugs 5/2011

01-10-2011 | PRECLINICAL STUDIES

NSC126188, a piperazine alkyl derivative, induces apoptosis via upregulation of RhoB in HeLa cells

Authors: Bo-Kyung Kim, Dong-Myung Kim, Kyung-Sook Chung, Song-Kyu Park, Shin-Jung Choi, Alexander Song, Kiho Lee, Chang-Woo Lee, Kyung-Bin Song, Gyoonhee Han, Julian Simon, Hwan Mook Kim, Misun Won

Published in: Investigational New Drugs | Issue 5/2011

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Summary

We describe here a piperazine alkyl derivative, NSC126188, which induced apoptosis of HeLa cells by upregulating RhoB expression. NSC126188 caused multi-septation of fission yeast and hypersensitized a ∆rho3 mutant, which implicates the involvement of functional human homolog RhoB. The treatment of cells with NSC126188 induced apoptosis and a dramatic increase in RhoB expression. In addition, RhoB knockdown using siRNA rescued cells from apoptosis, indicating a crucial role of RhoB in NSC126188-induced apoptosis. In a reporter assay using luciferase and EGFP under control of the RhoB promoter, NSC126188 increased both luciferase activity and the expression of EGFP, implicating transcriptional activation of RhoB by NSC126188. Furthermore, NSC126188 demonstrated in vivo anti-tumor activity, inhibiting tumor growth by 66.8% in a nude mouse xenograft using PC-3 human prostate cancer cells. These results suggest that NSC126188 is a potential lead compound and that upregulation of RhoB is associated with NSC126188-induced apoptosis.
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Metadata
Title
NSC126188, a piperazine alkyl derivative, induces apoptosis via upregulation of RhoB in HeLa cells
Authors
Bo-Kyung Kim
Dong-Myung Kim
Kyung-Sook Chung
Song-Kyu Park
Shin-Jung Choi
Alexander Song
Kiho Lee
Chang-Woo Lee
Kyung-Bin Song
Gyoonhee Han
Julian Simon
Hwan Mook Kim
Misun Won
Publication date
01-10-2011
Publisher
Springer US
Published in
Investigational New Drugs / Issue 5/2011
Print ISSN: 0167-6997
Electronic ISSN: 1573-0646
DOI
https://doi.org/10.1007/s10637-010-9433-3

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