We have located links that may give you full text access.
JOURNAL ARTICLE
RESEARCH SUPPORT, NON-U.S. GOV'T
Sensitization of hepatocellular carcinoma cells to Apo2L/TRAIL by a novel Akt/NF-κB signalling inhibitor.
Hepatocellular carcinoma (HCC) cells are intrinsically resistant to tumour necrosis factor-related apoptosis ligand (Apo2L/TRAIL), in part, due to the compensatory activation of nuclear factor-kappaB (NF-κB). To broaden the clinical utilization of Apo2L/TRAIL in HCC, OSU-A9, a potent indole-3-carbinol-derived Akt/NF-κB signalling inhibitor was used to overcome the intrinsic resistance. The antitumour effects of OSU-A9, Apo2L/TRAIL and the therapeutic combination were assessed by MTT assay, caspase activation and PARP cleavage, and the synergistic interactions were determined by Calcusyn analysis. NF-κB reporter gene and RT-PCR were tested for the activation of NF-κB and the expression of death receptors (DR)4 and 5. OSU-A9 could sensitize HCC cells to Apo2L/TRAIL with high potency through down-regulation of Akt/NF-κB signalling. OSU-A9 dose-dependently reduced Akt phosphorylation and the expression and nuclear localization of RelA/p65, accompanied by parallel decreases in the expression of NF-κB target products, including Bcl-xL, Mcl-1, cIAP1, cIAP2 and survivin. Moreover, OSU-A9 increased DR5 expression through a reactive oxygen species (ROS)-dependent mechanism. Concertedly, these mechanisms underlie the synergistic interaction between OSU-A9 and Apo2L/TRAIL in mediating apoptotic death in HCC cells. The ability of OSU-A9 to accentuate Apo2L/TRAIL-induced apoptosis by inactivating Akt/NF-κB signalling might foster a promising therapeutic strategy for HCC.
Full text links
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app
All material on this website is protected by copyright, Copyright © 1994-2024 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.
By using this service, you agree to our terms of use and privacy policy.
Your Privacy Choices
You can now claim free CME credits for this literature searchClaim now
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app