Quercetin enhances TRAIL-mediated apoptosis in colon cancer cells by inducing the accumulation of death receptors in lipid rafts

被引:151
作者
Psahoulia, Faiy H.
Drosopoulos, Konstantinos G.
Doubravska, Lenka
Andera, Ladislav
Pintzas, Alexander
机构
[1] Natl Hellen Res Fdn, Inst Biol Res & Biotechnol, Lab Signal Mediated Gene Express, Athens 11635, Greece
[2] Czech Acad Sci, Inst Mol Genet, Lab Cell Signaling & Apoptosis, Prague, Czech Republic
[3] Univ Thessaly, Sch Hlth Sci, Dept Med, Larisa, Greece
关键词
D O I
10.1158/1535-7163.MCT-07-0001
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Cytokines such as tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) can induce apoptosis in colon cancer cells through engagement of death receptors. Nevertheless, evading apoptosis induced by anticancer drugs characterizes many types of cancers. This results in the need for combination therapy. In this study, we have investigated whether the flavonoid quercetin could sensitize human colon adenocarcinoma cell lines to TRAIL-induced apoptosis. We report that quercetin enhanced TRAIL-induced apoptosis by causing the redistribution of DR4 and DR5 into lipid rafts. Nystatin, a cholesterol-sequestering agent, prevented quercetin-induced clustering of death receptors and sensitization to TRAIL-induced apoptosis in colon adenocarcinoma cells. In addition, our experiments show that quercetin, in combination with TRAIL, triggered the mitochondrial-dependent death pathway, as shown by Bid cleavage and the release of cytochrome c to the cytosol. Together, our findings propose that quercetin, through its ability to redistribute death receptors at the cell surface, facilitates death-inducing signaling complex formation and activation of caspases in response to death receptor stimulation. Based on these results, this study provides a challenging approach to enhance the efficiency of TRAIL-based therapies.
引用
收藏
页码:2591 / 2599
页数:9
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