Please use this identifier to cite or link to this item:
|Title:||Protein kinase C inhibition and X-linked inhibitor of apoptosis protein degradation contribute to the sensitization effect of luteolin on tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis in cancer cells||Authors:||Shi, R.-X.
|Issue Date:||1-Sep-2005||Citation:||Shi, R.-X., Ong, C.-N., Shen, H.-M. (2005-09-01). Protein kinase C inhibition and X-linked inhibitor of apoptosis protein degradation contribute to the sensitization effect of luteolin on tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis in cancer cells. Cancer Research 65 (17) : 7815-7823. ScholarBank@NUS Repository. https://doi.org/10.1158/0008-5472.CAN-04-3875||Abstract:||Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is an important member of the TNF superfamily with great potential in cancer therapy. Luteolin is a dietary flavonoid commonly found in some medicinal plants. Here we found that pretreatment with a noncytotoxic concentration of luteolin significantly sensitized TRAIL-induced apoptosis in both TRAIL-sensitive (HeLa) and TRAIL-resistant cancer cells (CNE1, HT29, and HepG2). Such sensitization is achieved through enhanced caspase-8 activation and caspase-3 maturation. Further, the protein level of X-linked inhibitor of apoptosis protein (XIAP) was markedly reduced in cells treated with luteolin and TRAIL, and ectopic expression of XIAP protected against cell death induced by luteolin and TRAIL, showing that luteolin sensitizes TRAIL-induced apoptosis through down-regulation of XIAP. In search of the molecular mechanism responsible for XIAP down-regulation, we found that luteolin and TRAIL promoted XIAP ubiquitination and proteasomal degradation. Next, we showed that protein kinase C (PKC) activation prevented cell death induced by luteolin and TRAIL via suppression of XIAP down-regulation. Moreover, luteolin inhibited PKC activity, and bisindolylmaleimide I, a general PKC inhibitor, simulated luteolin in sensitizing TRAIL-induced apoptosis. Taken together, these results present a novel anticancer effect of luteolin and support its potential application in cancer therapy in combination with TRAIL. In addition, our data reveal a new function of PKC in cell death: PKC activation stabilizes XIAP and thus suppresses TRAIL-induced apoptosis. ©2005 American Association for Cancer Research.||Source Title:||Cancer Research||URI:||http://scholarbank.nus.edu.sg/handle/10635/113614||ISSN:||00085472||DOI:||10.1158/0008-5472.CAN-04-3875|
|Appears in Collections:||Staff Publications|
Show full item record
Files in This Item:
There are no files associated with this item.
checked on Jan 27, 2023
WEB OF SCIENCETM
checked on Jan 18, 2023
checked on Jan 26, 2023
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.