Parvifloron D-based potential therapy for glioblastoma: Inducing apoptosis via the mitochondria dependent pathway
Authors
Magalhães, Mariana; Domínguez Martín, Eva María; Jorge, Joana; Gonçalves, Ana Cristina; Díaz Lanza, Ana María; [et al.]Identifiers
Permanent link (URI): http://hdl.handle.net/10017/59951DOI: 10.3389/fphar.2022.1006832
ISSN: 1663-9812
Date
2022-10-12Funders
Fundação para a Ciência e a Tecnologia (FCT)
Bibliographic citation
Frontiers in Pharmacology, 2022, v. 13, n. 1006832, p. 1-12
Keywords
glioblastoma
Plectranthus spp
abietane diterpenes
antitumor activity
molecular mechanisms
Project
info:eu-repo/grantAgreement/FCT//UIDB%2F04539%2F2020/PO/
info:eu-repo/grantAgreement/FCT//UIDP%2F04539%2F2020/PO/
info:eu-repo/grantAgreement/FCT//LA%2FP%2F0058%2F2020(CIBB)/PO/
info:eu-repo/grantAgreement/FCT//UIDB%2F04567%2F2020/PO/
info:eu-repo/grantAgreement/FCT//UIDP%2F04567%2F2020/PO/
Document type
info:eu-repo/semantics/article
Version
info:eu-repo/semantics/publishedVersion
Rights
© 2022 The Authors
Attribution 4.0 International (CC BY 4.0)
Access rights
info:eu-repo/semantics/openAccess
Abstract
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 mitochondriadependent 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
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