Cargando…

Evodiamine Induces Apoptosis and Enhances TRAIL-Induced Apoptosis in Human Bladder Cancer Cells through mTOR/S6K1-Mediated Downregulation of Mcl-1

The tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), either alone or in combination with other anti-cancer agents, has been considered as a new strategy for anti-cancer therapy. In this study, we demonstrated that evodiamine, a quinolone alkaloid isolated from the fruit of Evodia fru...

Descripción completa

Detalles Bibliográficos
Autores principales: Zhang, Tao, Qu, Shanna, Shi, Qi, He, Dalin, Jin, Xunbo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Molecular Diversity Preservation International (MDPI) 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3958903/
https://www.ncbi.nlm.nih.gov/pubmed/24566141
http://dx.doi.org/10.3390/ijms15023154
_version_ 1782307967646826496
author Zhang, Tao
Qu, Shanna
Shi, Qi
He, Dalin
Jin, Xunbo
author_facet Zhang, Tao
Qu, Shanna
Shi, Qi
He, Dalin
Jin, Xunbo
author_sort Zhang, Tao
collection PubMed
description The tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), either alone or in combination with other anti-cancer agents, has been considered as a new strategy for anti-cancer therapy. In this study, we demonstrated that evodiamine, a quinolone alkaloid isolated from the fruit of Evodia fructus, induced apoptosis and enhanced TRAIL-induced apoptosis in human bladder cancer cells. To elucidate the underlying mechanism, we found that evodiamine significantly reduced the protein levels of Mcl-1 in 253J and T24 bladder cancer cells, and overexpression of this molecule attenuated the apoptosis induced by evodiamine alone, or in combination with TRAIL. Further experiments revealed that evodiamine did not affect the mRNA level, proteasomal degradation and protein stability of Mcl-1. On the other hand, evodiamine inhibited the mTOR/S6K1 pathway, which usually regulates protein translation; moreover, knockdown of S6K1 with small interfering RNA (siRNA) effectively reduced Mcl-1 levels, indicating evodiamine downregulates c-FLIP through inhibition of mTOR/S6K1 pathway. Taken together, our results indicate that evodiamine induces apoptosis and enhances TRAIL-induced apoptosis possibly through mTOR/S6K1-mediated downregulation of Mcl-1; furthermore, these findings provide a rationale for the combined application of evodiamine with TRAIL in the treatment of bladder cancer.
format Online
Article
Text
id pubmed-3958903
institution National Center for Biotechnology Information
language English
publishDate 2014
publisher Molecular Diversity Preservation International (MDPI)
record_format MEDLINE/PubMed
spelling pubmed-39589032014-03-20 Evodiamine Induces Apoptosis and Enhances TRAIL-Induced Apoptosis in Human Bladder Cancer Cells through mTOR/S6K1-Mediated Downregulation of Mcl-1 Zhang, Tao Qu, Shanna Shi, Qi He, Dalin Jin, Xunbo Int J Mol Sci Article The tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), either alone or in combination with other anti-cancer agents, has been considered as a new strategy for anti-cancer therapy. In this study, we demonstrated that evodiamine, a quinolone alkaloid isolated from the fruit of Evodia fructus, induced apoptosis and enhanced TRAIL-induced apoptosis in human bladder cancer cells. To elucidate the underlying mechanism, we found that evodiamine significantly reduced the protein levels of Mcl-1 in 253J and T24 bladder cancer cells, and overexpression of this molecule attenuated the apoptosis induced by evodiamine alone, or in combination with TRAIL. Further experiments revealed that evodiamine did not affect the mRNA level, proteasomal degradation and protein stability of Mcl-1. On the other hand, evodiamine inhibited the mTOR/S6K1 pathway, which usually regulates protein translation; moreover, knockdown of S6K1 with small interfering RNA (siRNA) effectively reduced Mcl-1 levels, indicating evodiamine downregulates c-FLIP through inhibition of mTOR/S6K1 pathway. Taken together, our results indicate that evodiamine induces apoptosis and enhances TRAIL-induced apoptosis possibly through mTOR/S6K1-mediated downregulation of Mcl-1; furthermore, these findings provide a rationale for the combined application of evodiamine with TRAIL in the treatment of bladder cancer. Molecular Diversity Preservation International (MDPI) 2014-02-21 /pmc/articles/PMC3958903/ /pubmed/24566141 http://dx.doi.org/10.3390/ijms15023154 Text en © 2014 by the authors; licensee MDPI, Basel, Switzerland http://creativecommons.org/licenses/by/3.0/ This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/).
spellingShingle Article
Zhang, Tao
Qu, Shanna
Shi, Qi
He, Dalin
Jin, Xunbo
Evodiamine Induces Apoptosis and Enhances TRAIL-Induced Apoptosis in Human Bladder Cancer Cells through mTOR/S6K1-Mediated Downregulation of Mcl-1
title Evodiamine Induces Apoptosis and Enhances TRAIL-Induced Apoptosis in Human Bladder Cancer Cells through mTOR/S6K1-Mediated Downregulation of Mcl-1
title_full Evodiamine Induces Apoptosis and Enhances TRAIL-Induced Apoptosis in Human Bladder Cancer Cells through mTOR/S6K1-Mediated Downregulation of Mcl-1
title_fullStr Evodiamine Induces Apoptosis and Enhances TRAIL-Induced Apoptosis in Human Bladder Cancer Cells through mTOR/S6K1-Mediated Downregulation of Mcl-1
title_full_unstemmed Evodiamine Induces Apoptosis and Enhances TRAIL-Induced Apoptosis in Human Bladder Cancer Cells through mTOR/S6K1-Mediated Downregulation of Mcl-1
title_short Evodiamine Induces Apoptosis and Enhances TRAIL-Induced Apoptosis in Human Bladder Cancer Cells through mTOR/S6K1-Mediated Downregulation of Mcl-1
title_sort evodiamine induces apoptosis and enhances trail-induced apoptosis in human bladder cancer cells through mtor/s6k1-mediated downregulation of mcl-1
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3958903/
https://www.ncbi.nlm.nih.gov/pubmed/24566141
http://dx.doi.org/10.3390/ijms15023154
work_keys_str_mv AT zhangtao evodiamineinducesapoptosisandenhancestrailinducedapoptosisinhumanbladdercancercellsthroughmtors6k1mediateddownregulationofmcl1
AT qushanna evodiamineinducesapoptosisandenhancestrailinducedapoptosisinhumanbladdercancercellsthroughmtors6k1mediateddownregulationofmcl1
AT shiqi evodiamineinducesapoptosisandenhancestrailinducedapoptosisinhumanbladdercancercellsthroughmtors6k1mediateddownregulationofmcl1
AT hedalin evodiamineinducesapoptosisandenhancestrailinducedapoptosisinhumanbladdercancercellsthroughmtors6k1mediateddownregulationofmcl1
AT jinxunbo evodiamineinducesapoptosisandenhancestrailinducedapoptosisinhumanbladdercancercellsthroughmtors6k1mediateddownregulationofmcl1