NSC126188, a piperazine alkyl derivative, induces apoptosis via upregulation of RhoB in HeLa cells.
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.
Kim
Bo-Kyung
BK
Medical Genomics Research Center, KRIBB, Daejeon 305-806, South Korea.
Kim
Dong-Myung
DM
Chung
Kyung-Sook
KS
Park
Song-Kyu
SK
Choi
Shin-Jung
SJ
Song
Alexander
A
Lee
Kiho
K
Lee
Chang-Woo
CW
Song
Kyung-Bin
KB
Han
Gyoonhee
G
Simon
Julian
J
Kim
Hwan Mook
HM
Won
Misun
M
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D017930:Genes, Reporter / Q000235:genetics; D006238:Haploidy; D006367:HeLa Cells; D006801:Humans; D008297:Male; D051379:Mice; D009154:Mutation / Q000235:genetics; D000077489:Piperazine; D010879:Piperazines / Q000737:chemistry / Q000494:pharmacology*; D011401:Promoter Regions, Genetic / Q000235:genetics; D011471:Prostatic Neoplasms / Q000473:pathology; D012568:Schizosaccharomyces / Q000187:drug effects / Q000254:growth & development; D015854:Up-Regulation / Q000187:drug effects*; D023041:Xenograft Model Antitumor Assays; D020743:rhoB GTP-Binding Protein / Q000235:genetics*
C558305:4-hexadecanoyl-1,1-dimethylpiperazin-1-ium; D010879:Piperazines; D000077489:Piperazine; D020743:rhoB GTP-Binding Protein