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Cordycepin induces apoptosis by caveolin-1-mediated JNK regulation of Foxo3a in human lung adenocarcinoma

Forkhead transcription factor (Foxo3a) is a downstream effector of JNK-induced tumor suppression. However, it is not clear whether the caveolin-1 (CAV1)-mediated JNK/Foxo3a pathway is involved in cancer cell apoptosis. We found that cordycepin upregulates CAV1 expression, which was accompanied by JN...

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Autores principales: Joo, Jong Cheon, Hwang, Jung Hoo, Jo, Eunbi, Kim, Young-Rang, Kim, Dae Joon, Lee, Kyung-Bok, Park, Soo Jung, Jang, Ik-Soon
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5355338/
https://www.ncbi.nlm.nih.gov/pubmed/28099944
http://dx.doi.org/10.18632/oncotarget.14661
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author Joo, Jong Cheon
Hwang, Jung Hoo
Jo, Eunbi
Kim, Young-Rang
Kim, Dae Joon
Lee, Kyung-Bok
Park, Soo Jung
Jang, Ik-Soon
author_facet Joo, Jong Cheon
Hwang, Jung Hoo
Jo, Eunbi
Kim, Young-Rang
Kim, Dae Joon
Lee, Kyung-Bok
Park, Soo Jung
Jang, Ik-Soon
author_sort Joo, Jong Cheon
collection PubMed
description Forkhead transcription factor (Foxo3a) is a downstream effector of JNK-induced tumor suppression. However, it is not clear whether the caveolin-1 (CAV1)-mediated JNK/Foxo3a pathway is involved in cancer cell apoptosis. We found that cordycepin upregulates CAV1 expression, which was accompanied by JNK phosphorylation (p-JNK) and subsequent Foxo3a translocation into the nucleus, resulting in the upregulation of Bax protein expression. Furthermore, we found that CAV1 overexpression upregulated p-JNK, whereas CAV1 siRNA downregulated p-JNK. Additionally, SP600125, a specific JNK inhibitor, significantly increased Foxo3a phosphorylation, which downregulated Foxo3a translocation into the nucleus, indicating that CAV1 mediates JNK regulation of Foxo3a. Foxo3a siRNA downregulated Bax protein and attenuated A549 apoptosis, indicating that the CAV1-mediated JNK/Foxo3a pathway induces the apoptosis of A549 lung cancer cells. Cordycepin significantly decreased tumor volume in nude mice. Taken together, these results indicate that cordycepin promotes CAV1 upregulation to enhance JNK/Foxo3a signaling pathway activation, inducing apoptosis in lung cancer cells, and support its potential as a therapeutic agent for lung cancer.
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spelling pubmed-53553382017-04-26 Cordycepin induces apoptosis by caveolin-1-mediated JNK regulation of Foxo3a in human lung adenocarcinoma Joo, Jong Cheon Hwang, Jung Hoo Jo, Eunbi Kim, Young-Rang Kim, Dae Joon Lee, Kyung-Bok Park, Soo Jung Jang, Ik-Soon Oncotarget Research Paper Forkhead transcription factor (Foxo3a) is a downstream effector of JNK-induced tumor suppression. However, it is not clear whether the caveolin-1 (CAV1)-mediated JNK/Foxo3a pathway is involved in cancer cell apoptosis. We found that cordycepin upregulates CAV1 expression, which was accompanied by JNK phosphorylation (p-JNK) and subsequent Foxo3a translocation into the nucleus, resulting in the upregulation of Bax protein expression. Furthermore, we found that CAV1 overexpression upregulated p-JNK, whereas CAV1 siRNA downregulated p-JNK. Additionally, SP600125, a specific JNK inhibitor, significantly increased Foxo3a phosphorylation, which downregulated Foxo3a translocation into the nucleus, indicating that CAV1 mediates JNK regulation of Foxo3a. Foxo3a siRNA downregulated Bax protein and attenuated A549 apoptosis, indicating that the CAV1-mediated JNK/Foxo3a pathway induces the apoptosis of A549 lung cancer cells. Cordycepin significantly decreased tumor volume in nude mice. Taken together, these results indicate that cordycepin promotes CAV1 upregulation to enhance JNK/Foxo3a signaling pathway activation, inducing apoptosis in lung cancer cells, and support its potential as a therapeutic agent for lung cancer. Impact Journals LLC 2017-01-14 /pmc/articles/PMC5355338/ /pubmed/28099944 http://dx.doi.org/10.18632/oncotarget.14661 Text en Copyright: © 2017 Joo et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Joo, Jong Cheon
Hwang, Jung Hoo
Jo, Eunbi
Kim, Young-Rang
Kim, Dae Joon
Lee, Kyung-Bok
Park, Soo Jung
Jang, Ik-Soon
Cordycepin induces apoptosis by caveolin-1-mediated JNK regulation of Foxo3a in human lung adenocarcinoma
title Cordycepin induces apoptosis by caveolin-1-mediated JNK regulation of Foxo3a in human lung adenocarcinoma
title_full Cordycepin induces apoptosis by caveolin-1-mediated JNK regulation of Foxo3a in human lung adenocarcinoma
title_fullStr Cordycepin induces apoptosis by caveolin-1-mediated JNK regulation of Foxo3a in human lung adenocarcinoma
title_full_unstemmed Cordycepin induces apoptosis by caveolin-1-mediated JNK regulation of Foxo3a in human lung adenocarcinoma
title_short Cordycepin induces apoptosis by caveolin-1-mediated JNK regulation of Foxo3a in human lung adenocarcinoma
title_sort cordycepin induces apoptosis by caveolin-1-mediated jnk regulation of foxo3a in human lung adenocarcinoma
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5355338/
https://www.ncbi.nlm.nih.gov/pubmed/28099944
http://dx.doi.org/10.18632/oncotarget.14661
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