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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...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2018
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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. |
format | Online Article Text |
id | pubmed-6099973 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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