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 journalArticle

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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 languageEnglish
Pages (from-to)853-860
Number of pages8
JournalInvestigational New Drugs
Volume29
Issue number5
DOIs
Publication statusPublished - 2011 Oct 1

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4-hexadecanoyl-1,1-dimethylpiperazin-1-ium
HeLa Cells
Up-Regulation
Apoptosis
Luciferases
piperazine
Schizosaccharomyces

All Science Journal Classification (ASJC) codes

  • Oncology
  • Pharmacology
  • Pharmacology (medical)

Cite this

Kim, B. K., Kim, D. M., Chung, K. S., Park, S. K., Choi, S. J., Song, A., ... Won, M. (2011). NSC126188, a piperazine alkyl derivative, induces apoptosis via upregulation of RhoB in HeLa cells. Investigational New Drugs, 29(5), 853-860. https://doi.org/10.1007/s10637-010-9433-3
Kim, Bo Kyung ; 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. / NSC126188, a piperazine alkyl derivative, induces apoptosis via upregulation of RhoB in HeLa cells. In: Investigational New Drugs. 2011 ; Vol. 29, No. 5. pp. 853-860.
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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.",
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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 2011, 'NSC126188, a piperazine alkyl derivative, induces apoptosis via upregulation of RhoB in HeLa cells', Investigational New Drugs, vol. 29, no. 5, pp. 853-860. https://doi.org/10.1007/s10637-010-9433-3

NSC126188, a piperazine alkyl derivative, induces apoptosis via upregulation of RhoB in HeLa cells. / Kim, Bo Kyung; 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.

In: Investigational New Drugs, Vol. 29, No. 5, 01.10.2011, p. 853-860.

Research output: Contribution to journalArticle

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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

PY - 2011/10/1

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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.

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