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

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

doi:10.1007/s10637-010-9433-3

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

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

Research output: Contribution to journal › Article › peer-review

9 Citations (Scopus)

Abstract

We describe here a piperazine alkyl derivative, NSC126188, which induced apoptosis of HeLa cells by upregulating RhoB expression. NSC126188 caused multiseptation of fission yeast and hypersensitized a Δrho3 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.

Original language	English
Pages (from-to)	853-860
Number of pages	8
Journal	Investigational New Drugs
Volume	29
Issue number	5
DOIs	https://doi.org/10.1007/s10637-010-9433-3
Publication status	Published - 2011 Oct

Bibliographical note

Funding Information:
Acknowledgments We are grateful to Young-Joo Jang and Hyunji Lee for their technical assistances. This work was supported in part by grants from the 21st Century Frontier for Functional Analysis of the Human Genome and the KRIBB Initiative from the Korea Research Council of Fundamental Science and Technology.

All Science Journal Classification (ASJC) codes

Oncology
Pharmacology
Pharmacology (medical)

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1007/s10637-010-9433-3

Cite this

@article{7bb18617c3394a75a07094a02833a5b9,

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

abstract = "We describe here a piperazine alkyl derivative, NSC126188, which induced apoptosis of HeLa cells by upregulating RhoB expression. NSC126188 caused multiseptation of fission yeast and hypersensitized a Δrho3 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.",

author = "Kim, {Bo Kyung} and Kim, {Dong Myung} and Chung, {Kyung Sook} and Park, {Song Kyu} and Choi, {Shin Jung} and Alexander Song and Kiho Lee and Lee, {Chang Woo} and Song, {Kyung Bin} and Gyoonhee Han and Julian Simon and Kim, {Hwan Mook} and Misun Won",

note = "Funding Information: Acknowledgments We are grateful to Young-Joo Jang and Hyunji Lee for their technical assistances. This work was supported in part by grants from the 21st Century Frontier for Functional Analysis of the Human Genome and the KRIBB Initiative from the Korea Research Council of Fundamental Science and Technology.",

year = "2011",

month = oct,

doi = "10.1007/s10637-010-9433-3",

language = "English",

volume = "29",

pages = "853--860",

journal = "Investigational New Drugs",

issn = "0167-6997",

publisher = "Kluwer Academic Publishers",

number = "5",

}

TY - JOUR

T1 - NSC126188, a piperazine alkyl derivative, induces apoptosis via upregulation of RhoB in HeLa cells

AU - Kim, Bo Kyung

AU - Kim, Dong Myung

AU - Chung, Kyung Sook

AU - Park, Song Kyu

AU - Choi, Shin Jung

AU - Song, Alexander

AU - Lee, Kiho

AU - Lee, Chang Woo

AU - Song, Kyung Bin

AU - Han, Gyoonhee

AU - Simon, Julian

AU - Kim, Hwan Mook

AU - Won, Misun

N1 - Funding Information: Acknowledgments We are grateful to Young-Joo Jang and Hyunji Lee for their technical assistances. This work was supported in part by grants from the 21st Century Frontier for Functional Analysis of the Human Genome and the KRIBB Initiative from the Korea Research Council of Fundamental Science and Technology.

PY - 2011/10

Y1 - 2011/10

N2 - We describe here a piperazine alkyl derivative, NSC126188, which induced apoptosis of HeLa cells by upregulating RhoB expression. NSC126188 caused multiseptation of fission yeast and hypersensitized a Δrho3 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.

AB - We describe here a piperazine alkyl derivative, NSC126188, which induced apoptosis of HeLa cells by upregulating RhoB expression. NSC126188 caused multiseptation of fission yeast and hypersensitized a Δrho3 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.

UR - http://www.scopus.com/inward/record.url?scp=84859898659&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84859898659&partnerID=8YFLogxK

U2 - 10.1007/s10637-010-9433-3

DO - 10.1007/s10637-010-9433-3

M3 - Article

C2 - 20432054

AN - SCOPUS:84859898659

SN - 0167-6997

VL - 29

SP - 853

EP - 860

JO - Investigational New Drugs

JF - Investigational New Drugs

IS - 5

ER -

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

Abstract

Bibliographical note

All Science Journal Classification (ASJC) codes

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this