Maritoclax Enhances TRAIL-Induced Apoptosis via CHOP-Mediated Upregulation of DR5 and miR-708-Mediated Downregulation of cFLIP

被引：19

作者：

Jeon, Mi-Yeon ^{[1
]}

Min, Kyoung-jin ^{[1
]}

Woo, Seon Min ^{[1
]}

Seo, Seung Un ^{[1
]}

Choi, Yung Hyun ^{[2
]}

Kim, Sang Hyun ^{[3
]}

Kim, Dong Eun ^{[4
]}

Lee, Tae-Jin ^{[5
]}

Kim, Shin ^{[1
]}

Park, Jong-Wook ^{[1
]}

Kwon, Taeg Kyu ^{[1
]}

机构：

[1] Keimyung Univ, Sch Med, Dept Immunol, 2800 Dalgubeoldaero, Daegu 704701, South Korea

[2] Dong Eui Univ, Dept Biochem, Coll Oriental Med, Busan 609735, South Korea

[3] Kyungpook Natl Univ, Dept Pharmacol, Sch Med, Taegu 702701, South Korea

[4] Keimyung Univ, Sch Med, Dept Otolaryngol, 2800 Dalgubeoldaero, Daegu 704701, South Korea

[5] Yeungnam Univ, Dept Anat, Coll Med, Daegu 705802, South Korea

来源：

MOLECULES | 2018年 / 23卷 / 11期

关键词：

maritoclax; TRAIL; cFLIP; DR5; MicroRNA; ER stress; CANCER CELLS; C-FLIP; DEATH; EXPRESSION; RESISTANCE; LIGAND; INHIBITION; CARCINOMA; RECEPTOR; MCL-1;

D O I：

10.3390/molecules23113030

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Maritoclax, an active constituent isolated from marine bacteria, has been known to induce Mcl-1 downregulation through proteasomal degradation. In this study, we investigated the sensitizing effect of maritoclax on tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis in human renal carcinoma cells. We found that combined treatment with maritoclax and TRAIL markedly induced apoptosis in renal carcinoma (Caki, ACHN and A498), lung cancer (A549) and hepatocellular carcinoma (SK-Hep1) cells. The upregulation of death receptor 5 (DR5) and downregulation of cellular FLICE-inhibitory protein (cFLIP) were involved in maritoclax plus TRAIL-induced apoptosis. Maritoclax-induced DR5 upregulation was regulated by induction of C/EBP homologous protein (CHOP) expression. Interestingly, maritoclax induced cFLIP downregulation through the increased expression of miR-708. Ectopic expression of cFLIP prevented combined maritoclax and TRAIL-induced apoptosis. Taken together, maritoclax sensitized TRAIL-induced apoptosis through CHOP-mediated DR5 upregulation and miR-708-mediated cFLIP downregulation.

引用

页数：13

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