Unveiling the antitumor mechanism of 7α-acetoxy-6β-hydroxyroyleanone from Plectranthus hadiensis in glioblastoma.

Autor: Magalhães M; University of Coimbra, Institute for Interdisciplinary Research, Doctoral Programme in Experimental Biology and Biomedicine (PDBEB), Portugal; University of Coimbra, CNC-Center for Neuroscience and Cell Biology, Coimbra, Portugal; University of Coimbra, Coimbra Institute for Clinical and Biomedical Research (iCBR), Clinic Academic Center of Coimbra (CACC), Faculty of Medicine, Coimbra, Portugal; University of Coimbra, Center for Innovative Biomedicine and Biotechnology (CIBB), Coimbra, Portugal., Domínguez-Martín EM; CBIOS-Universidade Lusófona's Research Center for Biosciences & Health Technologies, Lisbon, Portugal; Departamento de Ciencias Biomédicas, Facultad de Farmacia, Universidad de Alcalá de Henares, Madrid, Spain., Jorge J; University of Coimbra, Laboratory of Oncobiology and Hematology, University Clinic of Hematology and Applied Molecular Biology, Faculty of Medicine, Coimbra, Portugal; University of Coimbra, ICBR, Group of Environment Genetics and Oncobiology (CIMAGO)-Faculty of Medicine, Coimbra, Portugal., Gonçalves AC; University of Coimbra, Laboratory of Oncobiology and Hematology, University Clinic of Hematology and Applied Molecular Biology, Faculty of Medicine, Coimbra, Portugal; University of Coimbra, ICBR, Group of Environment Genetics and Oncobiology (CIMAGO)-Faculty of Medicine, Coimbra, Portugal., Massenzio F; Department of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy., Spigarelli R; Department of Biological, Geological and Environmental Sciences, University of Bologna, Bologna, Italy., Ribeiro-Rodrigues T; University of Coimbra, CNC-Center for Neuroscience and Cell Biology, Coimbra, Portugal; University of Coimbra, Coimbra Institute for Clinical and Biomedical Research (iCBR), Clinic Academic Center of Coimbra (CACC), Faculty of Medicine, Coimbra, Portugal; University of Coimbra, Center for Innovative Biomedicine and Biotechnology (CIBB), Coimbra, Portugal., Catarino S; University of Coimbra, Coimbra Institute for Clinical and Biomedical Research (iCBR), Clinic Academic Center of Coimbra (CACC), Faculty of Medicine, Coimbra, Portugal; University of Coimbra, Center for Innovative Biomedicine and Biotechnology (CIBB), Coimbra, Portugal., Girão H; University of Coimbra, Coimbra Institute for Clinical and Biomedical Research (iCBR), Clinic Academic Center of Coimbra (CACC), Faculty of Medicine, Coimbra, Portugal; University of Coimbra, Center for Innovative Biomedicine and Biotechnology (CIBB), Coimbra, Portugal., Monti B; Department of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy., Spisni E; Department of Biological, Geological and Environmental Sciences, University of Bologna, Bologna, Italy., Ferreira L; University of Coimbra, CNC-Center for Neuroscience and Cell Biology, Coimbra, Portugal; University of Coimbra, Center for Innovative Biomedicine and Biotechnology (CIBB), Coimbra, Portugal; University of Coimbra, Faculty of Medicine, Coimbra, Portugal., Oliveira PJ; University of Coimbra, CNC-Center for Neuroscience and Cell Biology, Coimbra, Portugal; University of Coimbra, Center for Innovative Biomedicine and Biotechnology (CIBB), Coimbra, Portugal., Efferth T; Department of Pharmaceutical Biology, Institute of Pharmaceutical and Biomedical Sciences, Johannes Gutenberg University, Mainz, Germany., Rijo P; CBIOS-Universidade Lusófona's Research Center for Biosciences & Health Technologies, Lisbon, Portugal; Faculty of Pharmacy, Instituto de Investigação Do Medicamento (iMed.ULisboa), University of Lisbon, Lisbon, Portugal., Cabral C; University of Coimbra, Coimbra Institute for Clinical and Biomedical Research (iCBR), Clinic Academic Center of Coimbra (CACC), Faculty of Medicine, Coimbra, Portugal; University of Coimbra, Center for Innovative Biomedicine and Biotechnology (CIBB), Coimbra, Portugal; University of Coimbra, Centre for Functional Ecology, Department of Life Sciences, Coimbra, Portugal. Electronic address: celia.cabral@fmed.uc.pt.
Jazyk: angličtina
Zdroj: Journal of ethnopharmacology [J Ethnopharmacol] 2024 Dec 05; Vol. 335, pp. 118689. Date of Electronic Publication: 2024 Aug 14.
DOI: 10.1016/j.jep.2024.118689
Abstrakt: Ethnopharmacological Relevance: Glioblastoma (GB) is the most aggressive and prevalent glioma within the central nervous system. Despite considerable efforts, GB continues to exhibit a dismal 5-year survival rate (∼6%). This is largely attributed to unfavorable prognosis and lack of viable treatment options. Therefore, novel therapies centered around plant-derived compounds emerge as a compelling avenue to enhance patient survival and well-being. The South African species, Plectranthus hadiensis Schweinf. (P. hadiensis), a member of the Lamiaceae family, has a history of use in traditional medicine for treating a range of diseases, including respiratory, digestive, and liver disorders. This species exhibits diverse biological activities, such as anti-inflammatory and antitumoral properties, likely attributed to its rich composition of naturally occurring diterpenes, like the abietane diterpene, 7α-acetoxy-6β-hydroxyroyleanone (Roy). Roy has demonstrated promising antitumor effects in various cancer cell lines, making it a compelling candidate for further investigation into its mechanisms against GB.
Aim of the Study: This study aims to investigate the antitumor activity and potential mechanism of Roy, a natural lead compound, in GB cells.
Material and Methods: Roy was isolated from the acetonic extract of P. hadiensis and its antitumor mechanism was assessed in a panel of human GB cell lines (U87, A172, H4, U373, and U118) to mimic tumor heterogeneity. Briefly, the impact of Roy treatment on the metabolic activity of cells was evaluated by Alamar Blue® assay, while cell death, cell cycle regulation, mitochondrial membrane potential, and activated caspase-3 activity were evaluated by flow cytometry. Measurement of mRNA levels of target genes was performed by qPCR, while protein expression was assessed by Western blotting. Cell uptake and impact on mitochondrial morphology were evaluated by confocal microscopy.
Results: Roy induced G 2 /M cell cycle arrest, mitochondrial fragmentation, and apoptosis by inhibiting the expression of anti-apoptotic proteins and increasing the levels of activated caspase-3. The concentrations of Roy needed to achieve significant inhibitory outcomes were notably lower (6-9 fold) than those of temozolomide (TMZ), the standard first-line treatment, for achieving comparable effects. In addition, at low concentrations (16 μM), Roy affected the metabolic activity of tumor cells while having no significant impact on non-tumoral cells (microglia and astrocytes).
Conclusion: Overall, Roy demonstrated a robust antitumor activity against GB cells offering a promising avenue for the development of novel chemotherapeutic approaches.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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