Carcinogenesis Advance Access originally published online on June 13, 2006
Carcinogenesis 2006 27(11):2223-2234; doi:10.1093/carcin/bgl087
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Phenethyl isothiocyanate-induced apoptosis in PC-3 human prostate cancer cells is mediated by reactive oxygen species-dependent disruption of the mitochondrial membrane potential
Departments of Pharmacology and University of Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine Pittsburgh, PA, USA
*To whom correspondence should be addressed. Tel: +1 412 623 3263; Fax: +1 412 623 7828; E-mail: singhs{at}upmc.edu
The present study was undertaken to gain insights into the molecular mechanism of apoptosis induction by phenethyl isothiocyanate (PEITC), which is a cancer chemopreventive constituent of cruciferous vegetables, using PC-3 human prostate cancer cells as a model. The PEITC-induced cell death in PC-3 cells was associated with disruption of the mitochondrial membrane potential, release of apoptogenic molecules (cytochrome c and Smac/DIABLO) from mitochondria to the cytosol and generation of reactive oxygen species (ROS), which were blocked in the presence of a combined mimetic of superoxide dismutase and catalase (Euk134). Ectopic expression of Bcl-xL, whose protein level is reduced markedly on treatment of PC-3 cells with PEITC, conferred partial protection against PEITC-induced apoptosis only at higher drug concentrations (>10 µM). Administration of 12 µmol PEITC/day (Monday through Friday) by oral gavage significantly retarded growth of PC-3 xenografts in athymic mice. For instance, 31 days after the initiation of PEITC administration, the average tumor volume in control mice (721 ± 153 mm3) was 
2-fold higher compared with mice receiving 12 µmol PEITC/day. The PEITC-mediated inhibition of PC-3 xenograft growth was associated with induction of Bax and Bid proteins. In conclusion, the present study indicates that the PEITC-induced apoptosis in PC-3 cells is mediated by ROS-dependent disruption of the mitochondrial membrane potential and regulated by Bax and Bid.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  A. Bommareddy, E.-R. Hahm, D. Xiao, A. A. Powolny, A. L. Fisher, Y. Jiang, and S. V. Singh Atg5 Regulates Phenethyl Isothiocyanate-Induced Autophagic and Apoptotic Cell Death in Human Prostate Cancer Cells Cancer Res., April 15, 2009; 69(8): 3704 - 3712. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Xiao, A. A. Powolny, and S. V. Singh Benzyl Isothiocyanate Targets Mitochondrial Respiratory Chain to Trigger Reactive Oxygen Species-dependent Apoptosis in Human Breast Cancer Cells J. Biol. Chem., October 31, 2008; 283(44): 30151 - 30163. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Wang, C. Li, D. Song, G. Zhao, L. Zhao, and Y. Jing Ethacrynic Acid Butyl-Ester Induces Apoptosis in Leukemia Cells through a Hydrogen Peroxide Mediated Pathway Independent of Glutathione S-Transferase P1-1 Inhibition Cancer Res., August 15, 2007; 67(16): 7856 - 7864. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Xiao and S. V. Singh Phenethyl Isothiocyanate Inhibits Angiogenesis In vitro and Ex vivo Cancer Res., March 1, 2007; 67(5): 2239 - 2246. [Abstract] [Full Text] [PDF]
|
|