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Sequesterpene Lactones Isolated from a Brazilian Cerrado Plant (Eremanthus spp.) as Anti-Proliferative Compounds, Characterized by Functional and Proteomic Analysis, Are Candidates for New Therapeutics in Glioblastoma

Gliomas are responsible for more than 60% of all primary brain tumors. Glioblastoma multiforme (GBM), a grade IV tumor (WHO), is one of the most frequent and malignant gliomas. Despite two decades of advances in the discovery of new markers for GBM, the chemotherapy of choice falls to temozolomide a...

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Autores principales: Izumi, Clarice, Laure, Helen Julie, Barbosa, Nayara Gonçalves, Hassibe Thomé, Carolina, Aguiar Ferreira, Germano, Paulo Barreto Sousa, João, Peporine Lopes, Norberto, César Rosa, José
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7369765/
https://www.ncbi.nlm.nih.gov/pubmed/32630308
http://dx.doi.org/10.3390/ijms21134713
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author Izumi, Clarice
Laure, Helen Julie
Barbosa, Nayara Gonçalves
Hassibe Thomé, Carolina
Aguiar Ferreira, Germano
Paulo Barreto Sousa, João
Peporine Lopes, Norberto
César Rosa, José
author_facet Izumi, Clarice
Laure, Helen Julie
Barbosa, Nayara Gonçalves
Hassibe Thomé, Carolina
Aguiar Ferreira, Germano
Paulo Barreto Sousa, João
Peporine Lopes, Norberto
César Rosa, José
author_sort Izumi, Clarice
collection PubMed
description Gliomas are responsible for more than 60% of all primary brain tumors. Glioblastoma multiforme (GBM), a grade IV tumor (WHO), is one of the most frequent and malignant gliomas. Despite two decades of advances in the discovery of new markers for GBM, the chemotherapy of choice falls to temozolomide after surgery and radiotherapy, which are not enough to increase the survival of patients to more than 15 months. It is urgent to discover new anti-glioma compounds. Many compounds derived from natural products have been used in the development of anti-tumor drugs. In this work, we have screened six low molecular weight sesquiterpene lactones, isolated from Eremanthus spp., and studied their function as anti-proliferative agents against GBM strains. We demonstrated that two of them, goyazensolide and lychnofolide, were effective in reducing cell viability, preventing the formation of anchorage-dependent colony and were able to pass through a mimetic blood-brain barrier making them candidates for glioma therapy, being more potent than temozolomide, according to in vitro assays for the cell lines tested. Proteomic analysis revealed a number of altered proteins involved in glycolytic metabolism and cellular catabolism.
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spelling pubmed-73697652020-07-21 Sequesterpene Lactones Isolated from a Brazilian Cerrado Plant (Eremanthus spp.) as Anti-Proliferative Compounds, Characterized by Functional and Proteomic Analysis, Are Candidates for New Therapeutics in Glioblastoma Izumi, Clarice Laure, Helen Julie Barbosa, Nayara Gonçalves Hassibe Thomé, Carolina Aguiar Ferreira, Germano Paulo Barreto Sousa, João Peporine Lopes, Norberto César Rosa, José Int J Mol Sci Article Gliomas are responsible for more than 60% of all primary brain tumors. Glioblastoma multiforme (GBM), a grade IV tumor (WHO), is one of the most frequent and malignant gliomas. Despite two decades of advances in the discovery of new markers for GBM, the chemotherapy of choice falls to temozolomide after surgery and radiotherapy, which are not enough to increase the survival of patients to more than 15 months. It is urgent to discover new anti-glioma compounds. Many compounds derived from natural products have been used in the development of anti-tumor drugs. In this work, we have screened six low molecular weight sesquiterpene lactones, isolated from Eremanthus spp., and studied their function as anti-proliferative agents against GBM strains. We demonstrated that two of them, goyazensolide and lychnofolide, were effective in reducing cell viability, preventing the formation of anchorage-dependent colony and were able to pass through a mimetic blood-brain barrier making them candidates for glioma therapy, being more potent than temozolomide, according to in vitro assays for the cell lines tested. Proteomic analysis revealed a number of altered proteins involved in glycolytic metabolism and cellular catabolism. MDPI 2020-07-01 /pmc/articles/PMC7369765/ /pubmed/32630308 http://dx.doi.org/10.3390/ijms21134713 Text en © 2020 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Izumi, Clarice
Laure, Helen Julie
Barbosa, Nayara Gonçalves
Hassibe Thomé, Carolina
Aguiar Ferreira, Germano
Paulo Barreto Sousa, João
Peporine Lopes, Norberto
César Rosa, José
Sequesterpene Lactones Isolated from a Brazilian Cerrado Plant (Eremanthus spp.) as Anti-Proliferative Compounds, Characterized by Functional and Proteomic Analysis, Are Candidates for New Therapeutics in Glioblastoma
title Sequesterpene Lactones Isolated from a Brazilian Cerrado Plant (Eremanthus spp.) as Anti-Proliferative Compounds, Characterized by Functional and Proteomic Analysis, Are Candidates for New Therapeutics in Glioblastoma
title_full Sequesterpene Lactones Isolated from a Brazilian Cerrado Plant (Eremanthus spp.) as Anti-Proliferative Compounds, Characterized by Functional and Proteomic Analysis, Are Candidates for New Therapeutics in Glioblastoma
title_fullStr Sequesterpene Lactones Isolated from a Brazilian Cerrado Plant (Eremanthus spp.) as Anti-Proliferative Compounds, Characterized by Functional and Proteomic Analysis, Are Candidates for New Therapeutics in Glioblastoma
title_full_unstemmed Sequesterpene Lactones Isolated from a Brazilian Cerrado Plant (Eremanthus spp.) as Anti-Proliferative Compounds, Characterized by Functional and Proteomic Analysis, Are Candidates for New Therapeutics in Glioblastoma
title_short Sequesterpene Lactones Isolated from a Brazilian Cerrado Plant (Eremanthus spp.) as Anti-Proliferative Compounds, Characterized by Functional and Proteomic Analysis, Are Candidates for New Therapeutics in Glioblastoma
title_sort sequesterpene lactones isolated from a brazilian cerrado plant (eremanthus spp.) as anti-proliferative compounds, characterized by functional and proteomic analysis, are candidates for new therapeutics in glioblastoma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7369765/
https://www.ncbi.nlm.nih.gov/pubmed/32630308
http://dx.doi.org/10.3390/ijms21134713
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