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PMID: 20432054 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

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

Investigational new drugs ·Vol. 29 ·No. 5 ·2011-10-00 ·Pages 853-60

Kim BK, Kim DM, Chung KS, Park SK, Choi SJ, Song A, Lee K, Lee CW, Song KB, Han G, Simon J, Kim HM, Won M

Abstract

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.

MeSH Terms
Animals Apoptosis/drug effects Cell Proliferation/drug effects Genes, Reporter/genetics Haploidy HeLa Cells Humans Male Mice Mutation/genetics Piperazine Piperazines/chemistry,pharmacology Promoter Regions, Genetic/genetics Prostatic Neoplasms/pathology Schizosaccharomyces/drug effects,growth & development Up-Regulation/drug effects Xenograft Model Antitumor Assays rhoB GTP-Binding Protein/genetics
Chemicals
4-hexadecanoyl-1,1-dimethylpiperazin-1-ium Piperazines Piperazine rhoB GTP-Binding Protein
Authors & Affiliations
13 authors, click to expand affiliations / ORCID
Kim Bo-Kyung
Medical Genomics Research Center, KRIBB, Daejeon 305-806, South Korea.
Kim Dong-Myung
Chung Kyung-Sook
Park Song-Kyu
Choi Shin-Jung
Song Alexander
Lee Kiho
Lee Chang-Woo
Song Kyung-Bin
Han Gyoonhee
Simon Julian
Kim Hwan Mook
Won Misun
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Article Info
Journal
Investigational new drugs
Abbr.
Invest New Drugs
ISSN
1573-0646
DOI
10.1007/s10637-010-9433-3
Published
2011-10-00
Epub
2010-00-30
Pages
853-60
Language
English
Region
United States
NLM ID
8309330
Subset
IM
External Links
PubMed source DOI: 10.1007/s10637-010-9433-3 View journal details
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