EHMT2 inhibitor BIX-01294 induces apoptosis through PMAIP1-USP9X-MCL1 axis in human bladder cancer cells

BIX-01294, an euchromatic histone-lysine N-methyltransferase 2 (EHMT2) inhibitor, has been reported to induce apoptosis in human neuroblastoma cells and inhibit the proliferation of bladder cancer cells. However, the definite mechanism of the apoptosis mediated by BIX-01294 in bladder cancer cells r...

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Autores principales: Cui, Jing, Sun, Wendong, Hao, Xuexi, Wei, Minli, Su, Xiaonan, Zhang, Yajing, Su, Ling, Liu, Xiangguo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2015
Materias:
Primary Research
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4326523/
https://www.ncbi.nlm.nih.gov/pubmed/25685062
http://dx.doi.org/10.1186/s12935-014-0149-x
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author Cui, Jing
Sun, Wendong
Hao, Xuexi
Wei, Minli
Su, Xiaonan
Zhang, Yajing
Su, Ling
Liu, Xiangguo
author_facet Cui, Jing
Sun, Wendong
Hao, Xuexi
Wei, Minli
Su, Xiaonan
Zhang, Yajing
Su, Ling
Liu, Xiangguo
author_sort Cui, Jing
collection PubMed
description BIX-01294, an euchromatic histone-lysine N-methyltransferase 2 (EHMT2) inhibitor, has been reported to induce apoptosis in human neuroblastoma cells and inhibit the proliferation of bladder cancer cells. However, the definite mechanism of the apoptosis mediated by BIX-01294 in bladder cancer cells remains unclear. In the present study, we found that BIX-01294 induced caspase-dependent apoptosis in human bladder cancer cells. Moreover, our data show BIX-01294 stimulates endoplasmic reticulum stress (ER stress) and up-regulated expression of PMAIP1 through DDIT3 up-regulation. Furthermore, down-regulation of the deubiquitinase USP9X by BIX-01294 results in downstream reduction of MCL1 expression, leading to apoptosis eventually. Thus, our findings demonstrate PMAIP1-USP9X-MCL1 axis may contribute to BIX-01294-induced apoptosis in human bladder cancer cells.
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spelling pubmed-43265232015-02-14 EHMT2 inhibitor BIX-01294 induces apoptosis through PMAIP1-USP9X-MCL1 axis in human bladder cancer cells Cui, Jing Sun, Wendong Hao, Xuexi Wei, Minli Su, Xiaonan Zhang, Yajing Su, Ling Liu, Xiangguo Cancer Cell Int Primary Research BIX-01294, an euchromatic histone-lysine N-methyltransferase 2 (EHMT2) inhibitor, has been reported to induce apoptosis in human neuroblastoma cells and inhibit the proliferation of bladder cancer cells. However, the definite mechanism of the apoptosis mediated by BIX-01294 in bladder cancer cells remains unclear. In the present study, we found that BIX-01294 induced caspase-dependent apoptosis in human bladder cancer cells. Moreover, our data show BIX-01294 stimulates endoplasmic reticulum stress (ER stress) and up-regulated expression of PMAIP1 through DDIT3 up-regulation. Furthermore, down-regulation of the deubiquitinase USP9X by BIX-01294 results in downstream reduction of MCL1 expression, leading to apoptosis eventually. Thus, our findings demonstrate PMAIP1-USP9X-MCL1 axis may contribute to BIX-01294-induced apoptosis in human bladder cancer cells. BioMed Central 2015-02-04 /pmc/articles/PMC4326523/ /pubmed/25685062 http://dx.doi.org/10.1186/s12935-014-0149-x Text en © Cui et al.; licensee BioMed Central. 2015 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Primary Research
Cui, Jing
Sun, Wendong
Hao, Xuexi
Wei, Minli
Su, Xiaonan
Zhang, Yajing
Su, Ling
Liu, Xiangguo
EHMT2 inhibitor BIX-01294 induces apoptosis through PMAIP1-USP9X-MCL1 axis in human bladder cancer cells
title EHMT2 inhibitor BIX-01294 induces apoptosis through PMAIP1-USP9X-MCL1 axis in human bladder cancer cells
title_full EHMT2 inhibitor BIX-01294 induces apoptosis through PMAIP1-USP9X-MCL1 axis in human bladder cancer cells
title_fullStr EHMT2 inhibitor BIX-01294 induces apoptosis through PMAIP1-USP9X-MCL1 axis in human bladder cancer cells
title_full_unstemmed EHMT2 inhibitor BIX-01294 induces apoptosis through PMAIP1-USP9X-MCL1 axis in human bladder cancer cells
title_short EHMT2 inhibitor BIX-01294 induces apoptosis through PMAIP1-USP9X-MCL1 axis in human bladder cancer cells
title_sort ehmt2 inhibitor bix-01294 induces apoptosis through pmaip1-usp9x-mcl1 axis in human bladder cancer cells
topic Primary Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4326523/
https://www.ncbi.nlm.nih.gov/pubmed/25685062
http://dx.doi.org/10.1186/s12935-014-0149-x
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