Unveiling the Antitumor Mechanism of 7α-Acetoxy-6β-Hydroxyroyleanone from Plectranthus hadiensis in Glioblastoma

Mariana Magalhães; Eva María Domínguez-Martín; Joana Jorge; Ana Cristina Gonçalves; Francesca Massenzio; Renato Spigarelli; Teresa Ribeiro-Rodrigues; Steve Catarino; Henrique Girão; Barbara Monti; Enzo Spisni; Lino Ferreira; Paulo J. Oliveira; Thomas Efferth; Patrícia Rijo; Célia Cabral

doi:10.20944/preprints202405.0775.v1

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preprints.org > medicine and pharmacology > pharmacology and toxicology > doi: 10.20944/preprints202405.0775.v1

Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Unveiling the Antitumor Mechanism of 7α-Acetoxy-6β-Hydroxyroyleanone from Plectranthus hadiensis in Glioblastoma

Mariana Magalhães

Eva María Domínguez-Martín

Joana Jorge

Ana Cristina Gonçalves

Francesca Massenzio

Renato Spigarelli

Teresa Ribeiro-Rodrigues

Version 1 : Received: 12 May 2024 / Approved: 12 May 2024 / Online: 13 May 2024 (08:23:46 CEST)

How to cite: Magalhães, M.; Domínguez-Martín, E. M.; Jorge, J.; Gonçalves, A. C.; Massenzio, F.; Spigarelli, R.; Ribeiro-Rodrigues, T.; Catarino, S.; Girão, H.; Monti, B.; Spisni, E.; Ferreira, L.; Oliveira, P. J.; Efferth, T.; Rijo, P.; Cabral, C. Unveiling the Antitumor Mechanism of 7α-Acetoxy-6β-Hydroxyroyleanone from Plectranthus hadiensis in Glioblastoma. Preprints 2024, 2024050775. https://doi.org/10.20944/preprints202405.0775.v1 Magalhães, M.; Domínguez-Martín, E. M.; Jorge, J.; Gonçalves, A. C.; Massenzio, F.; Spigarelli, R.; Ribeiro-Rodrigues, T.; Catarino, S.; Girão, H.; Monti, B.; Spisni, E.; Ferreira, L.; Oliveira, P. J.; Efferth, T.; Rijo, P.; Cabral, C. Unveiling the Antitumor Mechanism of 7α-Acetoxy-6β-Hydroxyroyleanone from Plectranthus hadiensis in Glioblastoma. Preprints 2024, 2024050775. https://doi.org/10.20944/preprints202405.0775.v1

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MDPI and ACS Style

Magalhães, M.; Domínguez-Martín, E. M.; Jorge, J.; Gonçalves, A. C.; Massenzio, F.; Spigarelli, R.; Ribeiro-Rodrigues, T.; Catarino, S.; Girão, H.; Monti, B.; Spisni, E.; Ferreira, L.; Oliveira, P. J.; Efferth, T.; Rijo, P.; Cabral, C. Unveiling the Antitumor Mechanism of 7α-Acetoxy-6β-Hydroxyroyleanone from Plectranthus hadiensis in Glioblastoma. Preprints 2024, 2024050775. https://doi.org/10.20944/preprints202405.0775.v1

APA Style

Magalhães, M., Domínguez-Martín, E. M., Jorge, J., Gonçalves, A. C., Massenzio, F., Spigarelli, R., Ribeiro-Rodrigues, T., Catarino, S., Girão, H., Monti, B., Spisni, E., Ferreira, L., Oliveira, P. J., Efferth, T., Rijo, P., & Cabral, C. (2024). Unveiling the Antitumor Mechanism of 7α-Acetoxy-6β-Hydroxyroyleanone from<em> Plectranthus hadiensis</em> in Glioblastoma. Preprints. https://doi.org/10.20944/preprints202405.0775.v1

Chicago/Turabian Style

Magalhães, M., Patrícia Rijo and Célia Cabral. 2024 "Unveiling the Antitumor Mechanism of 7α-Acetoxy-6β-Hydroxyroyleanone from<em> Plectranthus hadiensis</em> in Glioblastoma" Preprints. https://doi.org/10.20944/preprints202405.0775.v1

Abstract

Glioblastoma (GB) is the most aggressive and prevalent glioma within the Central Nervous System. GB exhibit a dismal 5-year survival rate (~6%) due to unfavorable prognosis and lack of viable treatment options. Therefore, novel therapies with plant-derived compounds emerge as very promising. This study aims to investigate the antitumor activity of 7α-acetoxy-6β-hydroxyroyleanone (Roy) in GB cell lines. Roy was isolated from Plectranthus hadiensis Schweinf. and its antitumor mechanism was assessed in a panel of five GB cell lines to mimic tumor heterogeneity. Metabolic activity was evaluated by Alamar Blue® assay, while cell death, cell cycle regulation, mitochondrial membrane potential, and activated caspase-3 were evaluated by flow cytometry. mRNA levels of target genes were measured by qPCR and protein expression was assessed by Western blotting. Cell uptake and impact on mitochondrial morphology were evaluated by confocal microscopy. Roy induced G2/M cell cycle arrest, mitochondrial fragmentation, and apoptosis by inhibiting the expression of anti-apoptotic proteins and increasing activated caspase-3 levels with concentration 6-9 fold lower than those of temozolomide, the first-line treatment. Roy demonstrated a robust antitumor activity against GB cells, without affecting non tumoral cells (microglia and astrocytes), being a promising natural lead compound for the development of novel chemotherapeutic approaches.

Keywords

Glioblastoma; Plectranthus hadiensis Schweinf; Royleanone; Abietane diterpenes; Antitumor activity

Subject

Medicine and Pharmacology, Pharmacology and Toxicology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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