Hispolon from Phellinus linteus induces apoptosis and sensitizes human cancer cells to the tumor necrosis factor-related apoptosis-inducing ligand through upregulation of death receptors

被引:28
作者
Kim, Ji-Hun [1 ,2 ]
Kim, Yu Chul [3 ]
Park, Byoungduck [4 ]
机构
[1] Konkuk Univ, Dept Biotechnol, Res Inst RIBHS, Chungju 27478, Chungbuk, South Korea
[2] Konkuk Univ, Coll Biomed & Hlth Sci, Chungju 27478, Chungbuk, South Korea
[3] Discovery Res Ctr, C&C Res Labs, Suwon 440746, Gyeonggi Do, South Korea
[4] Keimyung Univ, Coll Pharm, Daegu 704701, South Korea
基金
新加坡国家研究基金会;
关键词
TRAIL-induced apoptosis; hispolon; ERK; death receptor; c-FLIP; Bcl-2; TRAIL-INDUCED APOPTOSIS; TRAIL/APO2L-INDUCED APOPTOSIS; DOWN-REGULATION; PROTEIN; XIAP; EXPRESSION; INHIBITOR; CASPASE-8; RESISTANCE; INDUCTION;
D O I
10.3892/or.2015.4440
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a potent anticancer agent possessing the ability to induce apoptosis in various cancer cells but not in non-malignant cells. However, certain type of cancer cells are resistant to TRAIL-induced apoptosis and some acquire resistance after the first treatment. So development of an agent that can reduce or avoid resistance in TRAIL-induced apoptosis has garnered significant attention. The present study evaluated the anticancer potential of hispolon in TRAIL-induced apoptosis and indicated hispolon can sensitize cancer cells to TRAIL. As the mechanism of action was examined, hispolon was found to activate caspase-3, caspase-8 and caspase-9, while downregulating the expression of cell survival proteins such as cFLIP, Bcl-2 and Bcl-xL and upregulating the expression of Bax and truncated Bid. We also found hispolon induced death receptors in a non-cell type-specific manner. Upregulation of death receptors by hispolon was found to be p53-independent but linked to the induction of CAAT enhancer binding protein homologous protein (CHOP). Overall, hispolon was demonstrated to potentiate the apoptotic effects of TRAIL through downregulation of anti-apoptotic proteins and upregulation of death receptors linked with CHOP and pERK elevation.
引用
收藏
页码:1020 / 1026
页数:7
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