TY - JOUR
T1 - Selective killing of oncogenically transformed cells through a ROS-mediated mechanism by β-phenylethyl isothiocyanate
AU - Trachootham, Dunyaporn
AU - Zhou, Yan
AU - Zhang, Hui
AU - Demizu, Yusuke
AU - Chen, Zhao
AU - Pelicano, Helene
AU - Chiao, Paul J.
AU - Achanta, Geetha
AU - Arlinghaus, Ralph B.
AU - Liu, Jinsong
AU - Huang, Peng
N1 - Funding Information:
The authors thank Tian-ai Wu, Yumin Hu, and Min Du for technical assistance. This work was supported in part by grants CA085563, CA100428, CA109041, and CA16672 from the National Institutes of Health. D.T. is a recipient of a scholarship from the Anandamahidol Foundation under the royal patronage of His Majesty the King of Thailand.
PY - 2006/9
Y1 - 2006/9
N2 - Reactive oxygen species (ROS) stimulate cell proliferation and induce genetic instability, and their increase in cancer cells is often viewed as an adverse event. Here, we show that such abnormal increases in ROS can be exploited to selectively kill cancer cells using β-phenylethyl isothiocyanate (PEITC). Oncogenic transformation of ovarian epithelial cells with H-RasV12 or expression of Bcr-Abl in hematopoietic cells causes elevated ROS generation and renders the malignant cells highly sensitive to PEITC, which effectively disables the glutathione antioxidant system and causes severe ROS accumulation preferentially in the transformed cells due to their active ROS output. Excessive ROS causes oxidative mitochondrial damage, inactivation of redox-sensitive molecules, and massive cell death. In vivo, PEITC exhibits therapeutic activity and prolongs animal survival.
AB - Reactive oxygen species (ROS) stimulate cell proliferation and induce genetic instability, and their increase in cancer cells is often viewed as an adverse event. Here, we show that such abnormal increases in ROS can be exploited to selectively kill cancer cells using β-phenylethyl isothiocyanate (PEITC). Oncogenic transformation of ovarian epithelial cells with H-RasV12 or expression of Bcr-Abl in hematopoietic cells causes elevated ROS generation and renders the malignant cells highly sensitive to PEITC, which effectively disables the glutathione antioxidant system and causes severe ROS accumulation preferentially in the transformed cells due to their active ROS output. Excessive ROS causes oxidative mitochondrial damage, inactivation of redox-sensitive molecules, and massive cell death. In vivo, PEITC exhibits therapeutic activity and prolongs animal survival.
KW - CELLCYCLE
UR - http://www.scopus.com/inward/record.url?scp=33748146888&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33748146888&partnerID=8YFLogxK
U2 - 10.1016/j.ccr.2006.08.009
DO - 10.1016/j.ccr.2006.08.009
M3 - Article
C2 - 16959615
AN - SCOPUS:33748146888
SN - 1535-6108
VL - 10
SP - 241
EP - 252
JO - Cancer cell
JF - Cancer cell
IS - 3
ER -