Combinatorial treatment with natural compounds in prostate cancer inhibits prostate tumor growth and leads to key modulations of cancer cell metabolism

High-throughput screening of a natural compound library was performed to identify the most efficacious combinatorial treatment on prostate cancer. Ursolic acid, curcumin and resveratrol were selected for further analyses and administered in vivo via the diet, either alone or in combination, in a mou...

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Autores principales: Lodi, Alessia, Saha, Achinto, Lu, Xiyuan, Wang, Bo, Sentandreu, Enrique, Collins, Meghan, Kolonin, Mikhail G., DiGiovanni, John, Tiziani, Stefano
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5705091/
https://www.ncbi.nlm.nih.gov/pubmed/29202102
http://dx.doi.org/10.1038/s41698-017-0024-z
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author Lodi, Alessia
Saha, Achinto
Lu, Xiyuan
Wang, Bo
Sentandreu, Enrique
Collins, Meghan
Kolonin, Mikhail G.
DiGiovanni, John
Tiziani, Stefano
author_facet Lodi, Alessia
Saha, Achinto
Lu, Xiyuan
Wang, Bo
Sentandreu, Enrique
Collins, Meghan
Kolonin, Mikhail G.
DiGiovanni, John
Tiziani, Stefano
author_sort Lodi, Alessia
collection PubMed
description High-throughput screening of a natural compound library was performed to identify the most efficacious combinatorial treatment on prostate cancer. Ursolic acid, curcumin and resveratrol were selected for further analyses and administered in vivo via the diet, either alone or in combination, in a mouse allograft model of prostate cancer. All possible combinations of these natural compounds produced synergistic effects on tumor size and weight, as predicted in the screens. A subsequent untargeted metabolomics and metabolic flux analysis using isotopically labeled glutamine indicated that the compound combinations modulated glutamine metabolism. In addition, ASCT2 levels and STAT3, mTORC1 and AMPK activity were modulated to a greater extent by the combinations compared to the individual compounds. Overall, this approach can be useful for identifying synergistic combinations of natural compounds for chemopreventive and therapeutic interventions.
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spelling pubmed-57050912017-11-28 Combinatorial treatment with natural compounds in prostate cancer inhibits prostate tumor growth and leads to key modulations of cancer cell metabolism Lodi, Alessia Saha, Achinto Lu, Xiyuan Wang, Bo Sentandreu, Enrique Collins, Meghan Kolonin, Mikhail G. DiGiovanni, John Tiziani, Stefano NPJ Precis Oncol Article High-throughput screening of a natural compound library was performed to identify the most efficacious combinatorial treatment on prostate cancer. Ursolic acid, curcumin and resveratrol were selected for further analyses and administered in vivo via the diet, either alone or in combination, in a mouse allograft model of prostate cancer. All possible combinations of these natural compounds produced synergistic effects on tumor size and weight, as predicted in the screens. A subsequent untargeted metabolomics and metabolic flux analysis using isotopically labeled glutamine indicated that the compound combinations modulated glutamine metabolism. In addition, ASCT2 levels and STAT3, mTORC1 and AMPK activity were modulated to a greater extent by the combinations compared to the individual compounds. Overall, this approach can be useful for identifying synergistic combinations of natural compounds for chemopreventive and therapeutic interventions. Nature Publishing Group UK 2017-06-05 /pmc/articles/PMC5705091/ /pubmed/29202102 http://dx.doi.org/10.1038/s41698-017-0024-z Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Lodi, Alessia
Saha, Achinto
Lu, Xiyuan
Wang, Bo
Sentandreu, Enrique
Collins, Meghan
Kolonin, Mikhail G.
DiGiovanni, John
Tiziani, Stefano
Combinatorial treatment with natural compounds in prostate cancer inhibits prostate tumor growth and leads to key modulations of cancer cell metabolism
title Combinatorial treatment with natural compounds in prostate cancer inhibits prostate tumor growth and leads to key modulations of cancer cell metabolism
title_full Combinatorial treatment with natural compounds in prostate cancer inhibits prostate tumor growth and leads to key modulations of cancer cell metabolism
title_fullStr Combinatorial treatment with natural compounds in prostate cancer inhibits prostate tumor growth and leads to key modulations of cancer cell metabolism
title_full_unstemmed Combinatorial treatment with natural compounds in prostate cancer inhibits prostate tumor growth and leads to key modulations of cancer cell metabolism
title_short Combinatorial treatment with natural compounds in prostate cancer inhibits prostate tumor growth and leads to key modulations of cancer cell metabolism
title_sort combinatorial treatment with natural compounds in prostate cancer inhibits prostate tumor growth and leads to key modulations of cancer cell metabolism
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5705091/
https://www.ncbi.nlm.nih.gov/pubmed/29202102
http://dx.doi.org/10.1038/s41698-017-0024-z
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