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Lambertianic Acid Sensitizes Non-Small Cell Lung Cancers to TRAIL-Induced Apoptosis via Inhibition of XIAP/NF-κB and Activation of Caspases and Death Receptor 4

Lambertianic acid (LA) is a biologically active compound from the leaves of Pinus koraiensis. In the present study, apoptotic mechanisms of LA plus TNF-related apoptosis-inducing ligand (TRAIL) were elucidated in non-small cell lung cancer cells (NSCLCs). Cytotoxicity assay, flow cytometry, immunopr...

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Autores principales: Ahn, Deok Soo, Lee, Hyo Jung, Hwang, Jisung, Han, Hyukgyu, Kim, Bonglee, Shim, BumSang, Kim, Sung-Hoon
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5983579/
https://www.ncbi.nlm.nih.gov/pubmed/29772677
http://dx.doi.org/10.3390/ijms19051476
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author Ahn, Deok Soo
Lee, Hyo Jung
Hwang, Jisung
Han, Hyukgyu
Kim, Bonglee
Shim, BumSang
Kim, Sung-Hoon
author_facet Ahn, Deok Soo
Lee, Hyo Jung
Hwang, Jisung
Han, Hyukgyu
Kim, Bonglee
Shim, BumSang
Kim, Sung-Hoon
author_sort Ahn, Deok Soo
collection PubMed
description Lambertianic acid (LA) is a biologically active compound from the leaves of Pinus koraiensis. In the present study, apoptotic mechanisms of LA plus TNF-related apoptosis-inducing ligand (TRAIL) were elucidated in non-small cell lung cancer cells (NSCLCs). Cytotoxicity assay, flow cytometry, immunoprecipitation, and Western blotting were performed. Here, combined treatment of LA and TRAIL increased cytotoxicity, sub-G1 population, cleaved poly (ADP-ribose) polymerase (PARP), and caspase3/8/9 in A549 and H1299 cells compared to LA or TRAIL alone. Furthermore, combined treatment of LA and TRAIL significantly decreased antiapoptotic proteins such as B-cell lymphoma 2 (Bcl-2), Fas-like inhibitor protein (FLIP), and X-linked inhibitor of apoptosis protein (XIAP), and enhanced the activation of proapoptotic proteins Bid compared to LA or TRAIL alone. In addition, combined treatment of LA and TRAIL upregulated the expression of Death receptor 4 (DR4) and downregulated phosphorylation of nuclear factor κ-light-chain-enhancer of activated B cells (p-NF-κB), inhibitory protein of kB family (p-IκB), and FLIP in A549 and H1299 cells along with disrupted binding of XIAP with caspase3 or NF-κB. Overall, these findings suggest that lambertianic acid enhances TRAIL-induced apoptosis via inhibition of XIAP/NF-κB in TRAIL resistant NSCLCs.
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spelling pubmed-59835792018-06-05 Lambertianic Acid Sensitizes Non-Small Cell Lung Cancers to TRAIL-Induced Apoptosis via Inhibition of XIAP/NF-κB and Activation of Caspases and Death Receptor 4 Ahn, Deok Soo Lee, Hyo Jung Hwang, Jisung Han, Hyukgyu Kim, Bonglee Shim, BumSang Kim, Sung-Hoon Int J Mol Sci Article Lambertianic acid (LA) is a biologically active compound from the leaves of Pinus koraiensis. In the present study, apoptotic mechanisms of LA plus TNF-related apoptosis-inducing ligand (TRAIL) were elucidated in non-small cell lung cancer cells (NSCLCs). Cytotoxicity assay, flow cytometry, immunoprecipitation, and Western blotting were performed. Here, combined treatment of LA and TRAIL increased cytotoxicity, sub-G1 population, cleaved poly (ADP-ribose) polymerase (PARP), and caspase3/8/9 in A549 and H1299 cells compared to LA or TRAIL alone. Furthermore, combined treatment of LA and TRAIL significantly decreased antiapoptotic proteins such as B-cell lymphoma 2 (Bcl-2), Fas-like inhibitor protein (FLIP), and X-linked inhibitor of apoptosis protein (XIAP), and enhanced the activation of proapoptotic proteins Bid compared to LA or TRAIL alone. In addition, combined treatment of LA and TRAIL upregulated the expression of Death receptor 4 (DR4) and downregulated phosphorylation of nuclear factor κ-light-chain-enhancer of activated B cells (p-NF-κB), inhibitory protein of kB family (p-IκB), and FLIP in A549 and H1299 cells along with disrupted binding of XIAP with caspase3 or NF-κB. Overall, these findings suggest that lambertianic acid enhances TRAIL-induced apoptosis via inhibition of XIAP/NF-κB in TRAIL resistant NSCLCs. MDPI 2018-05-16 /pmc/articles/PMC5983579/ /pubmed/29772677 http://dx.doi.org/10.3390/ijms19051476 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
Ahn, Deok Soo
Lee, Hyo Jung
Hwang, Jisung
Han, Hyukgyu
Kim, Bonglee
Shim, BumSang
Kim, Sung-Hoon
Lambertianic Acid Sensitizes Non-Small Cell Lung Cancers to TRAIL-Induced Apoptosis via Inhibition of XIAP/NF-κB and Activation of Caspases and Death Receptor 4
title Lambertianic Acid Sensitizes Non-Small Cell Lung Cancers to TRAIL-Induced Apoptosis via Inhibition of XIAP/NF-κB and Activation of Caspases and Death Receptor 4
title_full Lambertianic Acid Sensitizes Non-Small Cell Lung Cancers to TRAIL-Induced Apoptosis via Inhibition of XIAP/NF-κB and Activation of Caspases and Death Receptor 4
title_fullStr Lambertianic Acid Sensitizes Non-Small Cell Lung Cancers to TRAIL-Induced Apoptosis via Inhibition of XIAP/NF-κB and Activation of Caspases and Death Receptor 4
title_full_unstemmed Lambertianic Acid Sensitizes Non-Small Cell Lung Cancers to TRAIL-Induced Apoptosis via Inhibition of XIAP/NF-κB and Activation of Caspases and Death Receptor 4
title_short Lambertianic Acid Sensitizes Non-Small Cell Lung Cancers to TRAIL-Induced Apoptosis via Inhibition of XIAP/NF-κB and Activation of Caspases and Death Receptor 4
title_sort lambertianic acid sensitizes non-small cell lung cancers to trail-induced apoptosis via inhibition of xiap/nf-κb and activation of caspases and death receptor 4
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5983579/
https://www.ncbi.nlm.nih.gov/pubmed/29772677
http://dx.doi.org/10.3390/ijms19051476
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