A novel antitumor piperazine alkyl compound causes apoptosis by inducing RhoB expression via ROS-mediated c-Abl/p38 MAPK signaling
- Authors
- Chung, Kyung-Sook; Han, Gyoonhee; Kim, Bo-Kyung; Kim, Hwan-Mook; Yang, Jee Sun; Ahn, Jiwon; Lee, Kyeong; Song, Kyung-Bin; Won, Misun
- Issue Date
- Dec-2013
- Publisher
- SPRINGER
- Keywords
- Prostate cancer; RhoB; ROS; c-Abl; p38 MAPK
- Citation
- CANCER CHEMOTHERAPY AND PHARMACOLOGY, v.72, no.6, pp.1315 - 1324
- Journal Title
- CANCER CHEMOTHERAPY AND PHARMACOLOGY
- Volume
- 72
- Number
- 6
- Start Page
- 1315
- End Page
- 1324
- URI
- https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/14078
- DOI
- 10.1007/s00280-013-2310-y
- ISSN
- 0344-5704
- Abstract
- 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. 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. 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. 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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