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α‐Mangostin‐encapsulated PLGA nanoparticles inhibit colorectal cancer growth by inhibiting Notch pathway
Colorectal cancer (CRC) is the fourth leading cause of cancer‐related mortality. Recent studies have stated that Notch signalling is highly activated in cancer stem cells (CSCs) and plays an important role in the development and progression of CRC. Like normal colorectal epithelium, CRCs are organiz...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7576287/ https://www.ncbi.nlm.nih.gov/pubmed/32830433 http://dx.doi.org/10.1111/jcmm.15731 |
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author | Chandra Boinpelly, Varun Verma, Raj K. Srivastav, Sudesh Srivastava, Rakesh K. Shankar, Sharmila |
author_facet | Chandra Boinpelly, Varun Verma, Raj K. Srivastav, Sudesh Srivastava, Rakesh K. Shankar, Sharmila |
author_sort | Chandra Boinpelly, Varun |
collection | PubMed |
description | Colorectal cancer (CRC) is the fourth leading cause of cancer‐related mortality. Recent studies have stated that Notch signalling is highly activated in cancer stem cells (CSCs) and plays an important role in the development and progression of CRC. Like normal colorectal epithelium, CRCs are organized hierarchically and include populations of CSCs. In order to enhance the biological activity of α‐mangostin, we formulated α‐mangostin‐encapsulated PLGA nanoparticles (Mang‐NPs) and examined the molecular mechanisms by which Mang‐NPs inhibit CRC cell viability, colony formation, epithelial‐mesenchymal transition (EMT) and induce apoptosis. Mang‐NPs inhibited cell viability, colony formation and induced apoptosis. Mang‐NPs also inhibited EMT by up‐regulating E‐cadherin and inhibiting N‐cadherin and transcription factors Snail, Slug and Zeb1. As dysregulated signalling through the Notch receptors promotes oncogenesis, we measured the effects of Mang‐NPs on Notch pathway. Mang‐NPs inhibited Notch signalling by suppressing the expression of Notch receptors (Notch1 and Notch2), their ligands (Jagged 1 and DLL4), γ‐secretase complex protein (Nicastrin) and downstream target (Hes‐1). Notch receptor signalling regulates cell fate determination in stem cell population. Finally, Mang‐NPs inhibited the self‐renewal capacity of CSCs, stem cell markers (CD133, CD44, Musashi and LGR5) and pluripotency maintaining factors (Oct4, Sox‐2, KLF‐4, c‐Myc and Nanog). Overall, our data suggest that Mang‐NPs can inhibit CRC growth, EMT and CSCs’ population by suppressing Notch pathway and its target. Therefore, Mang‐NPs can be used for the treatment and prevention of CRC. |
format | Online Article Text |
id | pubmed-7576287 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-75762872020-10-23 α‐Mangostin‐encapsulated PLGA nanoparticles inhibit colorectal cancer growth by inhibiting Notch pathway Chandra Boinpelly, Varun Verma, Raj K. Srivastav, Sudesh Srivastava, Rakesh K. Shankar, Sharmila J Cell Mol Med Original Articles Colorectal cancer (CRC) is the fourth leading cause of cancer‐related mortality. Recent studies have stated that Notch signalling is highly activated in cancer stem cells (CSCs) and plays an important role in the development and progression of CRC. Like normal colorectal epithelium, CRCs are organized hierarchically and include populations of CSCs. In order to enhance the biological activity of α‐mangostin, we formulated α‐mangostin‐encapsulated PLGA nanoparticles (Mang‐NPs) and examined the molecular mechanisms by which Mang‐NPs inhibit CRC cell viability, colony formation, epithelial‐mesenchymal transition (EMT) and induce apoptosis. Mang‐NPs inhibited cell viability, colony formation and induced apoptosis. Mang‐NPs also inhibited EMT by up‐regulating E‐cadherin and inhibiting N‐cadherin and transcription factors Snail, Slug and Zeb1. As dysregulated signalling through the Notch receptors promotes oncogenesis, we measured the effects of Mang‐NPs on Notch pathway. Mang‐NPs inhibited Notch signalling by suppressing the expression of Notch receptors (Notch1 and Notch2), their ligands (Jagged 1 and DLL4), γ‐secretase complex protein (Nicastrin) and downstream target (Hes‐1). Notch receptor signalling regulates cell fate determination in stem cell population. Finally, Mang‐NPs inhibited the self‐renewal capacity of CSCs, stem cell markers (CD133, CD44, Musashi and LGR5) and pluripotency maintaining factors (Oct4, Sox‐2, KLF‐4, c‐Myc and Nanog). Overall, our data suggest that Mang‐NPs can inhibit CRC growth, EMT and CSCs’ population by suppressing Notch pathway and its target. Therefore, Mang‐NPs can be used for the treatment and prevention of CRC. John Wiley and Sons Inc. 2020-08-23 2020-10 /pmc/articles/PMC7576287/ /pubmed/32830433 http://dx.doi.org/10.1111/jcmm.15731 Text en © 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd. This is an open access article under the terms of the 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 | Original Articles Chandra Boinpelly, Varun Verma, Raj K. Srivastav, Sudesh Srivastava, Rakesh K. Shankar, Sharmila α‐Mangostin‐encapsulated PLGA nanoparticles inhibit colorectal cancer growth by inhibiting Notch pathway |
title | α‐Mangostin‐encapsulated PLGA nanoparticles inhibit colorectal cancer growth by inhibiting Notch pathway |
title_full | α‐Mangostin‐encapsulated PLGA nanoparticles inhibit colorectal cancer growth by inhibiting Notch pathway |
title_fullStr | α‐Mangostin‐encapsulated PLGA nanoparticles inhibit colorectal cancer growth by inhibiting Notch pathway |
title_full_unstemmed | α‐Mangostin‐encapsulated PLGA nanoparticles inhibit colorectal cancer growth by inhibiting Notch pathway |
title_short | α‐Mangostin‐encapsulated PLGA nanoparticles inhibit colorectal cancer growth by inhibiting Notch pathway |
title_sort | α‐mangostin‐encapsulated plga nanoparticles inhibit colorectal cancer growth by inhibiting notch pathway |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7576287/ https://www.ncbi.nlm.nih.gov/pubmed/32830433 http://dx.doi.org/10.1111/jcmm.15731 |
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