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Titania‐Coated Gold Nano‐Bipyramids for Blocking Autophagy Flux and Sensitizing Cancer Cells to Proteasome Inhibitor‐Induced Death
Targeting protein degradation is recognized as a valid approach to cancer therapy. The ubiquitin–proteasome system (UPS) and the autophagy–lysosome pathway are two major pathways for intracellular protein degradation. Proteasome inhibitors such as bortezomib are clinically approved for treating mali...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5867123/ https://www.ncbi.nlm.nih.gov/pubmed/29593960 http://dx.doi.org/10.1002/advs.201700585 |
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author | Wan, Hong‐Ye Chen, Jian‐Li Zhu, Xingzhong Liu, Liang Wang, Jianfang Zhu, Xiao‐Ming |
author_facet | Wan, Hong‐Ye Chen, Jian‐Li Zhu, Xingzhong Liu, Liang Wang, Jianfang Zhu, Xiao‐Ming |
author_sort | Wan, Hong‐Ye |
collection | PubMed |
description | Targeting protein degradation is recognized as a valid approach to cancer therapy. The ubiquitin–proteasome system (UPS) and the autophagy–lysosome pathway are two major pathways for intracellular protein degradation. Proteasome inhibitors such as bortezomib are clinically approved for treating malignancies, but to date, they are still unsatisfactory for cancer therapy. This study identifies titania‐coated gold nano‐bipyramid (NBP/TiO(2)) nanostructures as an autophagic flux inhibitor, as the smallest NBP/TiO(2) nanostructures induce significant autophagosome accumulation in human glioblastoma U‐87 MG cells via blocking the autophagosome–lysosome fusion process and inhibiting lysosomal degradation. Further study indicates that NBP/TiO(2) nanostructures reduce the intracellular level of mature cathepsin B and directly inhibit the proteolytic activity of cathepsin B, thereby further inhibiting trypsin‐like proteolytic activity, which is a potential cotarget for UPS inhibition. NBP/TiO(2) nanostructures interact synergistically with bortezomib to suppress the viability of U‐87 MG cells, as the combined treatment synergistically induces the intracellular accumulation of ubiquitinated protein and endoplasmic reticulum stress. In addition, photothermal therapy further synergistically reduces the cell viability. In summary, this study suggests that NBP/TiO(2) nanostructures function as a promising anticancer agent in combination with proteasome inhibitors. |
format | Online Article Text |
id | pubmed-5867123 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-58671232018-03-28 Titania‐Coated Gold Nano‐Bipyramids for Blocking Autophagy Flux and Sensitizing Cancer Cells to Proteasome Inhibitor‐Induced Death Wan, Hong‐Ye Chen, Jian‐Li Zhu, Xingzhong Liu, Liang Wang, Jianfang Zhu, Xiao‐Ming Adv Sci (Weinh) Full Papers Targeting protein degradation is recognized as a valid approach to cancer therapy. The ubiquitin–proteasome system (UPS) and the autophagy–lysosome pathway are two major pathways for intracellular protein degradation. Proteasome inhibitors such as bortezomib are clinically approved for treating malignancies, but to date, they are still unsatisfactory for cancer therapy. This study identifies titania‐coated gold nano‐bipyramid (NBP/TiO(2)) nanostructures as an autophagic flux inhibitor, as the smallest NBP/TiO(2) nanostructures induce significant autophagosome accumulation in human glioblastoma U‐87 MG cells via blocking the autophagosome–lysosome fusion process and inhibiting lysosomal degradation. Further study indicates that NBP/TiO(2) nanostructures reduce the intracellular level of mature cathepsin B and directly inhibit the proteolytic activity of cathepsin B, thereby further inhibiting trypsin‐like proteolytic activity, which is a potential cotarget for UPS inhibition. NBP/TiO(2) nanostructures interact synergistically with bortezomib to suppress the viability of U‐87 MG cells, as the combined treatment synergistically induces the intracellular accumulation of ubiquitinated protein and endoplasmic reticulum stress. In addition, photothermal therapy further synergistically reduces the cell viability. In summary, this study suggests that NBP/TiO(2) nanostructures function as a promising anticancer agent in combination with proteasome inhibitors. John Wiley and Sons Inc. 2017-12-01 /pmc/articles/PMC5867123/ /pubmed/29593960 http://dx.doi.org/10.1002/advs.201700585 Text en © 2017 The Authors. Published by WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim This is an open access article under the terms of the Creative Commons Attribution (http://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Full Papers Wan, Hong‐Ye Chen, Jian‐Li Zhu, Xingzhong Liu, Liang Wang, Jianfang Zhu, Xiao‐Ming Titania‐Coated Gold Nano‐Bipyramids for Blocking Autophagy Flux and Sensitizing Cancer Cells to Proteasome Inhibitor‐Induced Death |
title | Titania‐Coated Gold Nano‐Bipyramids for Blocking Autophagy Flux and Sensitizing Cancer Cells to Proteasome Inhibitor‐Induced Death |
title_full | Titania‐Coated Gold Nano‐Bipyramids for Blocking Autophagy Flux and Sensitizing Cancer Cells to Proteasome Inhibitor‐Induced Death |
title_fullStr | Titania‐Coated Gold Nano‐Bipyramids for Blocking Autophagy Flux and Sensitizing Cancer Cells to Proteasome Inhibitor‐Induced Death |
title_full_unstemmed | Titania‐Coated Gold Nano‐Bipyramids for Blocking Autophagy Flux and Sensitizing Cancer Cells to Proteasome Inhibitor‐Induced Death |
title_short | Titania‐Coated Gold Nano‐Bipyramids for Blocking Autophagy Flux and Sensitizing Cancer Cells to Proteasome Inhibitor‐Induced Death |
title_sort | titania‐coated gold nano‐bipyramids for blocking autophagy flux and sensitizing cancer cells to proteasome inhibitor‐induced death |
topic | Full Papers |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5867123/ https://www.ncbi.nlm.nih.gov/pubmed/29593960 http://dx.doi.org/10.1002/advs.201700585 |
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