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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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
- Pharmacology (medical)