Format

Send to

Choose Destination
Biochem Pharmacol. 2010 Feb 1;79(3):350-60. doi: 10.1016/j.bcp.2009.09.006. Epub 2009 Sep 24.

Oleanane triterpenoid CDDO-Me inhibits growth and induces apoptosis in prostate cancer cells through a ROS-dependent mechanism.

Author information

1
Department of Surgery, Henry Ford Health System, Detroit, MI 48202, USA.

Abstract

CDDO-Me, a synthetic triterpenoid derived from oleanolic acid, is a promising anticancer agent that has shown strong activity against a wide variety of cancer types in vitro and in vivo. We have previously shown that CDDO-Me induces apoptosis in prostate cancer cells irrespective of their hormonal status. To further understand the proapoptotic mechanism of CDDO-Me, we investigated the role of reactive oxygen species (ROS) in mediating the apoptosis inducing activity of CDDO-Me in LNCaP and PC-3 prostate cancer cell lines. Here, we show that CDDO-Me induces ROS generation from both nonmitochondrial and mitochondrial sources, which is associated with the induction of apoptosis as characterized by increased annexin V-binding, cleavage of PARP-1 and procaspases-3, -8, -9, loss of mitochondrial membrane potential and release of cytochrome c. In addition, CDDO-Me inhibited cell survival Akt, NF-kappaB and mTOR signaling proteins. The inhibition of ROS generation by N-acetylcysteine (NAC) or by overexpression of antioxidant enzymes glutathione peroxidase (GPx) and superoxide dismutase-1 (SOD-1) prevented CDDO-Me-induced apoptosis. Pretreatment with NAC blocked annexin V-binding, cleavage of PARP-1 and procaspases-3, -8, -9, loss of mitochondrial membrane potential and release of cytochrome c by CDDO-Me. NAC also prevented the inhibition of constitutively active Akt, NF-kappaB and mTOR by CDDO-Me. Together, these data indicate that ROS plays an essential role in the induction of apoptosis by CDDO-Me in prostate cancer cells.

PMID:
19782051
PMCID:
PMC2822351
DOI:
10.1016/j.bcp.2009.09.006
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center