Maritoclax enhances TRAIL-induced apoptosis via CHOP-mediated upregulation of DR5 and miR-708-mediated downregulation of cFLIP

Mi Yeon Jeon; Kyoung jin Min; Seon Min Woo; Seung Un Seo; Yung Hyun Choi; Sang Hyun Kim; Dong Eun Kim; Tae Jin Lee; Shin Kim; Jong Wook Park; Taeg Kyu Kwon

doi:10.3390/molecules23113030

Maritoclax enhances TRAIL-induced apoptosis via CHOP-mediated upregulation of DR5 and miR-708-mediated downregulation of cFLIP

Mi Yeon Jeon, Kyoung jin Min, Seon Min Woo, Seung Un Seo, Yung Hyun Choi, Sang Hyun Kim, Dong Eun Kim, Tae Jin Lee, Shin Kim, Jong Wook Park, Taeg Kyu Kwon

Research output: Contribution to journal › Article › peer-review

22 Scopus citations

Abstract

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.

Original language	English
Article number	3030
Journal	Molecules
Volume	23
Issue number	11
DOIs	https://doi.org/10.3390/molecules23113030
State	Published - 20 Nov 2018

Keywords

DR5
ER stress
Maritoclax
MicroRNA
TRAIL
cFLIP

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.3390/molecules23113030

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title = "Maritoclax enhances TRAIL-induced apoptosis via CHOP-mediated upregulation of DR5 and miR-708-mediated downregulation of cFLIP",

abstract = "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.",

keywords = "DR5, ER stress, Maritoclax, MicroRNA, TRAIL, cFLIP",

author = "Jeon, \{Mi Yeon\} and Min, \{Kyoung jin\} and Woo, \{Seon Min\} and Seo, \{Seung Un\} and Choi, \{Yung Hyun\} and Kim, \{Sang Hyun\} and Kim, \{Dong Eun\} and Lee, \{Tae Jin\} and Shin Kim and Park, \{Jong Wook\} and Kwon, \{Taeg Kyu\}",

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doi = "10.3390/molecules23113030",

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T1 - Maritoclax enhances TRAIL-induced apoptosis via CHOP-mediated upregulation of DR5 and miR-708-mediated downregulation of cFLIP

AU - Jeon, Mi Yeon

AU - Min, Kyoung jin

AU - Woo, Seon Min

AU - Seo, Seung Un

AU - Choi, Yung Hyun

AU - Kim, Sang Hyun

AU - Kim, Dong Eun

AU - Lee, Tae Jin

AU - Kim, Shin

AU - Park, Jong Wook

AU - Kwon, Taeg Kyu

PY - 2018/11/20

Y1 - 2018/11/20

N2 - 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.

AB - 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.

KW - DR5

KW - ER stress

KW - Maritoclax

KW - MicroRNA

KW - TRAIL

KW - cFLIP

UR - https://www.scopus.com/pages/publications/85056955657

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DO - 10.3390/molecules23113030

M3 - Article

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AN - SCOPUS:85056955657

SN - 1420-3049

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IS - 11

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ER -

Maritoclax enhances TRAIL-induced apoptosis via CHOP-mediated upregulation of DR5 and miR-708-mediated downregulation of cFLIP

Abstract

Keywords

UN SDGs

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