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Curcumin Loaded Dendrimers Specifically Reduce Viability of Glioblastoma Cell Lines

Glioblastoma (GB) is a deadly and aggressive cancer of the CNS. Even with extensive resection and chemoradiotherapy, patient survival is still only 15 months. To maintain growth and proliferation, cancer cells require a high oxidative state. Curcumin, a well-known anti-inflammatory antioxidant, is a...

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Autores principales: Gallien, John, Srinageshwar, Bhairavi, Gallo, Kellie, Holtgrefe, Gretchen, Koneru, Sindhuja, Otero, Paulina Sequeiros, Bueno, Catalina Alvarez, Mosher, Jamie, Roh, Alison, Kohtz, D. Stave, Swanson, Douglas, Sharma, Ajit, Dunbar, Gary, Rossignol, Julien
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8512379/
https://www.ncbi.nlm.nih.gov/pubmed/34641594
http://dx.doi.org/10.3390/molecules26196050
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author Gallien, John
Srinageshwar, Bhairavi
Gallo, Kellie
Holtgrefe, Gretchen
Koneru, Sindhuja
Otero, Paulina Sequeiros
Bueno, Catalina Alvarez
Mosher, Jamie
Roh, Alison
Kohtz, D. Stave
Swanson, Douglas
Sharma, Ajit
Dunbar, Gary
Rossignol, Julien
author_facet Gallien, John
Srinageshwar, Bhairavi
Gallo, Kellie
Holtgrefe, Gretchen
Koneru, Sindhuja
Otero, Paulina Sequeiros
Bueno, Catalina Alvarez
Mosher, Jamie
Roh, Alison
Kohtz, D. Stave
Swanson, Douglas
Sharma, Ajit
Dunbar, Gary
Rossignol, Julien
author_sort Gallien, John
collection PubMed
description Glioblastoma (GB) is a deadly and aggressive cancer of the CNS. Even with extensive resection and chemoradiotherapy, patient survival is still only 15 months. To maintain growth and proliferation, cancer cells require a high oxidative state. Curcumin, a well-known anti-inflammatory antioxidant, is a potential candidate for treatment of GB. To facilitate efficient delivery of therapeutic doses of curcumin into cells, we encapsulated the drug in surface-modified polyamidoamine (PAMAM) dendrimers. We studied the in vitro effectiveness of a traditional PAMAM dendrimer (100% amine surface, G4 NH(2)), surface-modified dendrimer (10% amine and 90% hydroxyl-G4 90/10-Cys), and curcumin (Cur)-encapsulated dendrimer (G4 90/10-Cys-Cur) on three species of glioblastoma cell lines: mouse-GL261, rat-F98, and human-U87. Using an MTT assay for cell viability, we found that G4 90/10-Cys-Cur reduced viability of all three glioblastoma cell lines compared to non-cancerous control cells. Under similar conditions, unencapsulated curcumin was not effective, while the non-modified dendrimer (G4 NH(2)) caused significant death of both cancerous and normal cells. By harnessing and optimizing the components of PAMAM dendrimers, we are providing a promising new route for delivering cancer therapeutics. Our results with curcumin suggest that antioxidants are good candidates for treating glioblastoma.
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spelling pubmed-85123792021-10-14 Curcumin Loaded Dendrimers Specifically Reduce Viability of Glioblastoma Cell Lines Gallien, John Srinageshwar, Bhairavi Gallo, Kellie Holtgrefe, Gretchen Koneru, Sindhuja Otero, Paulina Sequeiros Bueno, Catalina Alvarez Mosher, Jamie Roh, Alison Kohtz, D. Stave Swanson, Douglas Sharma, Ajit Dunbar, Gary Rossignol, Julien Molecules Article Glioblastoma (GB) is a deadly and aggressive cancer of the CNS. Even with extensive resection and chemoradiotherapy, patient survival is still only 15 months. To maintain growth and proliferation, cancer cells require a high oxidative state. Curcumin, a well-known anti-inflammatory antioxidant, is a potential candidate for treatment of GB. To facilitate efficient delivery of therapeutic doses of curcumin into cells, we encapsulated the drug in surface-modified polyamidoamine (PAMAM) dendrimers. We studied the in vitro effectiveness of a traditional PAMAM dendrimer (100% amine surface, G4 NH(2)), surface-modified dendrimer (10% amine and 90% hydroxyl-G4 90/10-Cys), and curcumin (Cur)-encapsulated dendrimer (G4 90/10-Cys-Cur) on three species of glioblastoma cell lines: mouse-GL261, rat-F98, and human-U87. Using an MTT assay for cell viability, we found that G4 90/10-Cys-Cur reduced viability of all three glioblastoma cell lines compared to non-cancerous control cells. Under similar conditions, unencapsulated curcumin was not effective, while the non-modified dendrimer (G4 NH(2)) caused significant death of both cancerous and normal cells. By harnessing and optimizing the components of PAMAM dendrimers, we are providing a promising new route for delivering cancer therapeutics. Our results with curcumin suggest that antioxidants are good candidates for treating glioblastoma. MDPI 2021-10-06 /pmc/articles/PMC8512379/ /pubmed/34641594 http://dx.doi.org/10.3390/molecules26196050 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Gallien, John
Srinageshwar, Bhairavi
Gallo, Kellie
Holtgrefe, Gretchen
Koneru, Sindhuja
Otero, Paulina Sequeiros
Bueno, Catalina Alvarez
Mosher, Jamie
Roh, Alison
Kohtz, D. Stave
Swanson, Douglas
Sharma, Ajit
Dunbar, Gary
Rossignol, Julien
Curcumin Loaded Dendrimers Specifically Reduce Viability of Glioblastoma Cell Lines
title Curcumin Loaded Dendrimers Specifically Reduce Viability of Glioblastoma Cell Lines
title_full Curcumin Loaded Dendrimers Specifically Reduce Viability of Glioblastoma Cell Lines
title_fullStr Curcumin Loaded Dendrimers Specifically Reduce Viability of Glioblastoma Cell Lines
title_full_unstemmed Curcumin Loaded Dendrimers Specifically Reduce Viability of Glioblastoma Cell Lines
title_short Curcumin Loaded Dendrimers Specifically Reduce Viability of Glioblastoma Cell Lines
title_sort curcumin loaded dendrimers specifically reduce viability of glioblastoma cell lines
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8512379/
https://www.ncbi.nlm.nih.gov/pubmed/34641594
http://dx.doi.org/10.3390/molecules26196050
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