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Garcinol Enhances TRAIL-Induced Apoptotic Cell Death through Up-Regulation of DR5 and Down-Regulation of c-FLIP Expression

Garcinol is a polyisoprenylated benzophenone derived from the Garcinia indica fruit that possess potential therapeutic effects such as inhibition of inflammation and tumor expansion. Here, we investigated whether garcinol induces TRAIL sensitization in renal carcinoma cells. Single treatment with ga...

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Autores principales: Kim, Seok, Seo, Seung Un, Min, Kyoung-Jin, Woo, Seon Min, Nam, Ju-Ock, Kubatka, Peter, Kim, Shin, Park, Jong-Wook, Kwon, Taeg Kyu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6099973/
https://www.ncbi.nlm.nih.gov/pubmed/30004456
http://dx.doi.org/10.3390/molecules23071614
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author Kim, Seok
Seo, Seung Un
Min, Kyoung-Jin
Woo, Seon Min
Nam, Ju-Ock
Kubatka, Peter
Kim, Shin
Park, Jong-Wook
Kwon, Taeg Kyu
author_facet Kim, Seok
Seo, Seung Un
Min, Kyoung-Jin
Woo, Seon Min
Nam, Ju-Ock
Kubatka, Peter
Kim, Shin
Park, Jong-Wook
Kwon, Taeg Kyu
author_sort Kim, Seok
collection PubMed
description Garcinol is a polyisoprenylated benzophenone derived from the Garcinia indica fruit that possess potential therapeutic effects such as inhibition of inflammation and tumor expansion. Here, we investigated whether garcinol induces TRAIL sensitization in renal carcinoma cells. Single treatment with garcinol or TRAIL did not effect on apoptosis. However, combined treatment with garcinol plus TRAIL significantly induced apoptosis in renal carcinoma (Caki, ACHN and A498), lung carcinoma (A549), and hepatoma (SK-Hep1) cells. In contrast, garcinol plus TRAIL did not alter cell viability in normal cells. Garcinol plus TRAIL induced up-regulation of DR5 and down-regulation of c-FLIP expression at post-translational levels. Furthermore, knock-down of DR5 by siRNA and ectopic expression of c-FLIP blocked apoptotic cell death induced by garcinol plus TRAIL. Overall, our study provides evidence that garcinol can be exploited as a potential TRAIL sensitizer.
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spelling pubmed-60999732018-11-13 Garcinol Enhances TRAIL-Induced Apoptotic Cell Death through Up-Regulation of DR5 and Down-Regulation of c-FLIP Expression Kim, Seok Seo, Seung Un Min, Kyoung-Jin Woo, Seon Min Nam, Ju-Ock Kubatka, Peter Kim, Shin Park, Jong-Wook Kwon, Taeg Kyu Molecules Article Garcinol is a polyisoprenylated benzophenone derived from the Garcinia indica fruit that possess potential therapeutic effects such as inhibition of inflammation and tumor expansion. Here, we investigated whether garcinol induces TRAIL sensitization in renal carcinoma cells. Single treatment with garcinol or TRAIL did not effect on apoptosis. However, combined treatment with garcinol plus TRAIL significantly induced apoptosis in renal carcinoma (Caki, ACHN and A498), lung carcinoma (A549), and hepatoma (SK-Hep1) cells. In contrast, garcinol plus TRAIL did not alter cell viability in normal cells. Garcinol plus TRAIL induced up-regulation of DR5 and down-regulation of c-FLIP expression at post-translational levels. Furthermore, knock-down of DR5 by siRNA and ectopic expression of c-FLIP blocked apoptotic cell death induced by garcinol plus TRAIL. Overall, our study provides evidence that garcinol can be exploited as a potential TRAIL sensitizer. MDPI 2018-07-02 /pmc/articles/PMC6099973/ /pubmed/30004456 http://dx.doi.org/10.3390/molecules23071614 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Kim, Seok
Seo, Seung Un
Min, Kyoung-Jin
Woo, Seon Min
Nam, Ju-Ock
Kubatka, Peter
Kim, Shin
Park, Jong-Wook
Kwon, Taeg Kyu
Garcinol Enhances TRAIL-Induced Apoptotic Cell Death through Up-Regulation of DR5 and Down-Regulation of c-FLIP Expression
title Garcinol Enhances TRAIL-Induced Apoptotic Cell Death through Up-Regulation of DR5 and Down-Regulation of c-FLIP Expression
title_full Garcinol Enhances TRAIL-Induced Apoptotic Cell Death through Up-Regulation of DR5 and Down-Regulation of c-FLIP Expression
title_fullStr Garcinol Enhances TRAIL-Induced Apoptotic Cell Death through Up-Regulation of DR5 and Down-Regulation of c-FLIP Expression
title_full_unstemmed Garcinol Enhances TRAIL-Induced Apoptotic Cell Death through Up-Regulation of DR5 and Down-Regulation of c-FLIP Expression
title_short Garcinol Enhances TRAIL-Induced Apoptotic Cell Death through Up-Regulation of DR5 and Down-Regulation of c-FLIP Expression
title_sort garcinol enhances trail-induced apoptotic cell death through up-regulation of dr5 and down-regulation of c-flip expression
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6099973/
https://www.ncbi.nlm.nih.gov/pubmed/30004456
http://dx.doi.org/10.3390/molecules23071614
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