Cargando…

Parvifloron D-based potential therapy for glioblastoma: Inducing apoptosis via the mitochondria dependent pathway

Glioblastoma (GB) is the most malignant and frequent primary tumor of the central nervous system. The lack of diagnostic tools and the poor prognosis associated with this tumor type leads to restricted and limited options of treatment, namely surgical resection and radio-chemotherapy. However, despi...

Descripción completa

Detalles Bibliográficos
Autores principales: Magalhães, Mariana, Domínguez-Martín, Eva María, Jorge, Joana, Gonçalves, Ana Cristina, Díaz-Lanza, Ana María, Manadas, Bruno, Efferth, Thomas, Rijo, Patrícia, Cabral, Célia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9605735/
https://www.ncbi.nlm.nih.gov/pubmed/36313298
http://dx.doi.org/10.3389/fphar.2022.1006832
_version_ 1784818139403386880
author Magalhães, Mariana
Domínguez-Martín, Eva María
Jorge, Joana
Gonçalves, Ana Cristina
Díaz-Lanza, Ana María
Manadas, Bruno
Efferth, Thomas
Rijo, Patrícia
Cabral, Célia
author_facet Magalhães, Mariana
Domínguez-Martín, Eva María
Jorge, Joana
Gonçalves, Ana Cristina
Díaz-Lanza, Ana María
Manadas, Bruno
Efferth, Thomas
Rijo, Patrícia
Cabral, Célia
author_sort Magalhães, Mariana
collection PubMed
description Glioblastoma (GB) is the most malignant and frequent primary tumor of the central nervous system. The lack of diagnostic tools and the poor prognosis associated with this tumor type leads to restricted and limited options of treatment, namely surgical resection and radio-chemotherapy. However, despite these treatments, in almost all cases, patients experience relapse, leading to survival rates shorter than 5 years (∼15–18 months after diagnosis). Novel therapeutic approaches are urgently required (either by discovering new medicines or by repurposing drugs) to surpass the limitations of conventional treatments and improve patients’ survival rate and quality of life. In the present work, we investigated the antitumor potential of parvifloron D (ParvD), a drug lead of natural origin, in a GB cell line panel. This natural drug lead induced G2/M cell cycle arrest and apoptosis via activation of the intrinsic mitochondria-dependent pathway. Moreover, the necessary doses of ParvD to induce pronounced inhibitory effects were substantially lower than that of temozolomide (TMZ, first-line treatment) required to promote comparable effects. Therefore, ParvD may have the potential to overcome the resistance related to TMZ and contribute to the pursuit of hopeful treatments based on ParvD as a drug lead for future chemotherapeutics.
format Online
Article
Text
id pubmed-9605735
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-96057352022-10-27 Parvifloron D-based potential therapy for glioblastoma: Inducing apoptosis via the mitochondria dependent pathway Magalhães, Mariana Domínguez-Martín, Eva María Jorge, Joana Gonçalves, Ana Cristina Díaz-Lanza, Ana María Manadas, Bruno Efferth, Thomas Rijo, Patrícia Cabral, Célia Front Pharmacol Pharmacology Glioblastoma (GB) is the most malignant and frequent primary tumor of the central nervous system. The lack of diagnostic tools and the poor prognosis associated with this tumor type leads to restricted and limited options of treatment, namely surgical resection and radio-chemotherapy. However, despite these treatments, in almost all cases, patients experience relapse, leading to survival rates shorter than 5 years (∼15–18 months after diagnosis). Novel therapeutic approaches are urgently required (either by discovering new medicines or by repurposing drugs) to surpass the limitations of conventional treatments and improve patients’ survival rate and quality of life. In the present work, we investigated the antitumor potential of parvifloron D (ParvD), a drug lead of natural origin, in a GB cell line panel. This natural drug lead induced G2/M cell cycle arrest and apoptosis via activation of the intrinsic mitochondria-dependent pathway. Moreover, the necessary doses of ParvD to induce pronounced inhibitory effects were substantially lower than that of temozolomide (TMZ, first-line treatment) required to promote comparable effects. Therefore, ParvD may have the potential to overcome the resistance related to TMZ and contribute to the pursuit of hopeful treatments based on ParvD as a drug lead for future chemotherapeutics. Frontiers Media S.A. 2022-10-12 /pmc/articles/PMC9605735/ /pubmed/36313298 http://dx.doi.org/10.3389/fphar.2022.1006832 Text en Copyright © 2022 Magalhães, Domínguez-Martín, Jorge, Gonçalves, Díaz-Lanza, Manadas, Efferth, Rijo and Cabral. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Magalhães, Mariana
Domínguez-Martín, Eva María
Jorge, Joana
Gonçalves, Ana Cristina
Díaz-Lanza, Ana María
Manadas, Bruno
Efferth, Thomas
Rijo, Patrícia
Cabral, Célia
Parvifloron D-based potential therapy for glioblastoma: Inducing apoptosis via the mitochondria dependent pathway
title Parvifloron D-based potential therapy for glioblastoma: Inducing apoptosis via the mitochondria dependent pathway
title_full Parvifloron D-based potential therapy for glioblastoma: Inducing apoptosis via the mitochondria dependent pathway
title_fullStr Parvifloron D-based potential therapy for glioblastoma: Inducing apoptosis via the mitochondria dependent pathway
title_full_unstemmed Parvifloron D-based potential therapy for glioblastoma: Inducing apoptosis via the mitochondria dependent pathway
title_short Parvifloron D-based potential therapy for glioblastoma: Inducing apoptosis via the mitochondria dependent pathway
title_sort parvifloron d-based potential therapy for glioblastoma: inducing apoptosis via the mitochondria dependent pathway
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9605735/
https://www.ncbi.nlm.nih.gov/pubmed/36313298
http://dx.doi.org/10.3389/fphar.2022.1006832
work_keys_str_mv AT magalhaesmariana parviflorondbasedpotentialtherapyforglioblastomainducingapoptosisviathemitochondriadependentpathway
AT dominguezmartinevamaria parviflorondbasedpotentialtherapyforglioblastomainducingapoptosisviathemitochondriadependentpathway
AT jorgejoana parviflorondbasedpotentialtherapyforglioblastomainducingapoptosisviathemitochondriadependentpathway
AT goncalvesanacristina parviflorondbasedpotentialtherapyforglioblastomainducingapoptosisviathemitochondriadependentpathway
AT diazlanzaanamaria parviflorondbasedpotentialtherapyforglioblastomainducingapoptosisviathemitochondriadependentpathway
AT manadasbruno parviflorondbasedpotentialtherapyforglioblastomainducingapoptosisviathemitochondriadependentpathway
AT efferththomas parviflorondbasedpotentialtherapyforglioblastomainducingapoptosisviathemitochondriadependentpathway
AT rijopatricia parviflorondbasedpotentialtherapyforglioblastomainducingapoptosisviathemitochondriadependentpathway
AT cabralcelia parviflorondbasedpotentialtherapyforglioblastomainducingapoptosisviathemitochondriadependentpathway