Please use this identifier to cite or link to this item:
|Title:||Andrographolide sensitizes cancer cells to TRAIL-induced apoptosis via p53-mediated death receptor 4 up-regulation|
|Authors:||Zhou, J. |
|Citation:||Zhou, J., Lu, G.-D., Ong, C.-S., Ong, C.-N., Shen, H.-M. (2008). Andrographolide sensitizes cancer cells to TRAIL-induced apoptosis via p53-mediated death receptor 4 up-regulation. Molecular Cancer Therapeutics 7 (7) : 2170-2180. ScholarBank@NUS Repository. https://doi.org/10.1158/1535-7163.MCT-08-0071|
|Abstract:||Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is an importantmember of the tumor necrosis factor subfamily with great potential in cancer therapy. Andrographolide (Andro), a diterpenoid lactone isolated from a traditional herbal medicine Andrographis paniculata, is known to possess potent anti-inflammatory and anticancer activities. Here, we showed that pretreatment with Andro significantly enhances TRAIL-induced apoptosis in various human cancer cell lines, including those TRAIL-resistant cells. Such sensitization is achieved through transcriptional up-regulation of death receptor 4 (DR4), a death receptor of TRAIL. In search of the molecular mechanisms responsible for DR4 up-regulation, we found that the tumor suppressor p53 plays an essential role in DR4 transcriptional activation. Andro is capable of activating p53 via increased p53 phosphorylation and protein stabilization, a process mediated by enhanced reactive oxygen species production and subsequent c-Jun NH 2-terminal kinase activation. Pretreatment with an antioxidant (N-acetylcysteine) or a c-Jun NH2-terminal kinase inhibitor (SP600125) effectively prevented Andro-induced p53 activation and DR4 up-regulation and eventually blocked the Andro-induced sensitization on TRAIL-induced apoptosis. Taken together, these results present a novel anticancer effect of Andro and support its potential application in cancer therapy to overcome TRAIL resistance. Copyright © 2008 American Association for Cancer Research.|
|Source Title:||Molecular Cancer Therapeutics|
|Appears in Collections:||Staff Publications|
Show full item record
Files in This Item:
There are no files associated with this item.
checked on Sep 22, 2018
WEB OF SCIENCETM
checked on Sep 11, 2018
checked on Aug 3, 2018
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.