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Cancer Chemotherapy and Pharmacology
Published in: Cancer Chemotherapy and Pharmacology 6/2013

01-12-2013 | Original Article

A novel antitumor piperazine alkyl compound causes apoptosis by inducing RhoB expression via ROS-mediated c-Abl/p38 MAPK signaling

Authors: Kyung-Sook Chung, Gyoonhee Han, Bo-Kyung Kim, Hwan-Mook Kim, Jee Sun Yang, Jiwon Ahn, Kyeong Lee, Kyung-Bin Song, Misun Won

Published in: Cancer Chemotherapy and Pharmacology | Issue 6/2013

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Abstract

Purpose

We investigated the action mechanism of a novel anticancer compound, KR28 (1-allyl-4-dodecanoyl-1-ethyl-piperazin-1-ium; bromide), to induce apoptosis of human prostate carcinoma PC-3 cells.

Methods

To explore an apoptotic signaling of KR28, we used ROS assay, SRB assay, flow cytometry analysis, reporter assay, xenograft assay, Western blotting, and RT-PCR analysis.

Results

The growth inhibitory action of KR28 is cell line specific, impeding the growth of prostate carcinoma PC-3 and stomach carcinoma NUGC-3 cells. KR28 showed strong antitumor activity in PC-3 mouse xenograft model. KR28 increased ROS production, leading to nuclear c-Abl expression, which in turn activated p38 mitogen-activated protein kinase (MAPK) to enhance the expression of RhoB, an apoptosis inducer. The KR28-induced apoptosis was abrogated by the ROS scavenger N-acetylcysteine and by knockdown of c-Abl, p38 MAPK, or ATF2. Moreover, the p300 binding site and two CCAAT boxes in the RhoB promoter appear to be involved in ROS-mediated RhoB expression in the presence of KR28.

Conclusion

The antitumor agent KR28 induces apoptosis of PC-3 cells by ROS-mediated RhoB expression via c-Abl upregulation and activation of p38 MAPK/ATF-2.
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Metadata
Title
A novel antitumor piperazine alkyl compound causes apoptosis by inducing RhoB expression via ROS-mediated c-Abl/p38 MAPK signaling
Authors
Kyung-Sook Chung
Gyoonhee Han
Bo-Kyung Kim
Hwan-Mook Kim
Jee Sun Yang
Jiwon Ahn
Kyeong Lee
Kyung-Bin Song
Misun Won
Publication date
01-12-2013
Publisher
Springer Berlin Heidelberg
Published in
Cancer Chemotherapy and Pharmacology / Issue 6/2013
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI
https://doi.org/10.1007/s00280-013-2310-y

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