Glioblastoma (GB) is the most malignant form of primary astrocytoma, accounting for more than 60% of all brain tumors in adults. Nowadays, due to the development of multidrug resistance causing relapses to the current treatments and the development of severe side effects resulting in reduced survival rates, new therapeutic approaches are needed. The genus Plectranthus belongs to the Lamiaceae family and is known to be rich in abietane-type diterpenes, which possess antitumor activity. Specifically, P. hadiensis (Forssk.) Schweinf. ex Sprenger has been documented for the use against brain tumors. Therefore, the aim of this work was to perform the bioguided isolation of compounds from the acetonic extract of P. hadiensis stems and to investigate the in vitro antiglioblastoma activity of the extract and its isolated constituents. After extraction, six fractions were obtained from the acetonic extract of P. hadiensis stems. In a preliminary biological screening, the fractions V and III showed the highest antioxidant and antimicrobial activities. None of the fractions were toxic in the Artemia salina assay. We obtained different abietane-type diterpenes such as 7α-acetoxy-6β-hydroxyroyleanone (Roy) and 6β,7β-dihydroxyroyleanone (DiRoy), which was also in agreement with the HPLC-DAD profile of the extract. Furthermore, the antiproliferative activity was assessed in a glioma tumor cell line panel by the Alamar blue assay. After 48 h treatment, Roy exerted strong antiproliferative/cytotoxic effects against tumor cells with low IC50 values among the different cell lines. Finally, we synthesized a new fluorescence derivative in this study to evaluate the biodistribution of Roy. The uptake of BODIPY-7α-acetoxy-6β-hydroxyroyleanone by GB cells was associated with increased intracellular fluorescence, supporting the antiproliferative effects of Roy. In conclusion, Roy is a promising natural compound that may serve as a lead compound for further derivatization to develop future therapeutic strategies against GB.

Phytochemical Study and Antiglioblastoma Activity Assessment of Plectranthus hadiensis (Forssk.) Schweinf. ex Sprenger var. hadiensis Stems / E.M. Domínguez-Martín, M. Magalhães, A.M. Díaz-Lanza, M.P. Marques, S. Princiotto, A.M. Gómez, T. Efferth, C. Cabral, P. Rijo. - In: MOLECULES. - ISSN 1420-3049. - 27:12(2022 Jun 14), pp. 3813.1-3813.1. [10.3390/molecules27123813]

Phytochemical Study and Antiglioblastoma Activity Assessment of Plectranthus hadiensis (Forssk.) Schweinf. ex Sprenger var. hadiensis Stems

S. Princiotto;
2022

Abstract

Glioblastoma (GB) is the most malignant form of primary astrocytoma, accounting for more than 60% of all brain tumors in adults. Nowadays, due to the development of multidrug resistance causing relapses to the current treatments and the development of severe side effects resulting in reduced survival rates, new therapeutic approaches are needed. The genus Plectranthus belongs to the Lamiaceae family and is known to be rich in abietane-type diterpenes, which possess antitumor activity. Specifically, P. hadiensis (Forssk.) Schweinf. ex Sprenger has been documented for the use against brain tumors. Therefore, the aim of this work was to perform the bioguided isolation of compounds from the acetonic extract of P. hadiensis stems and to investigate the in vitro antiglioblastoma activity of the extract and its isolated constituents. After extraction, six fractions were obtained from the acetonic extract of P. hadiensis stems. In a preliminary biological screening, the fractions V and III showed the highest antioxidant and antimicrobial activities. None of the fractions were toxic in the Artemia salina assay. We obtained different abietane-type diterpenes such as 7α-acetoxy-6β-hydroxyroyleanone (Roy) and 6β,7β-dihydroxyroyleanone (DiRoy), which was also in agreement with the HPLC-DAD profile of the extract. Furthermore, the antiproliferative activity was assessed in a glioma tumor cell line panel by the Alamar blue assay. After 48 h treatment, Roy exerted strong antiproliferative/cytotoxic effects against tumor cells with low IC50 values among the different cell lines. Finally, we synthesized a new fluorescence derivative in this study to evaluate the biodistribution of Roy. The uptake of BODIPY-7α-acetoxy-6β-hydroxyroyleanone by GB cells was associated with increased intracellular fluorescence, supporting the antiproliferative effects of Roy. In conclusion, Roy is a promising natural compound that may serve as a lead compound for further derivatization to develop future therapeutic strategies against GB.
Lamiaceae; Plectranthus; cancer; diterpenes; glioblastoma; phytochemical; royleanones; Abietanes; Humans; Phytochemicals; Plant Extracts; Tissue Distribution; Brain Neoplasms; Plectranthus
Settore CHIM/06 - Chimica Organica
Settore CHIM/08 - Chimica Farmaceutica
14-giu-2022
https://www.mdpi.com/1420-3049/27/12/3813
Article (author)
File in questo prodotto:
File Dimensione Formato  
molecules-27-03813-v2.pdf

accesso aperto

Descrizione: Article
Tipologia: Publisher's version/PDF
Dimensione 1.79 MB
Formato Adobe PDF
1.79 MB Adobe PDF Visualizza/Apri
Pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/969440
Citazioni
  • ???jsp.display-item.citation.pmc??? 1
  • Scopus 6
  • ???jsp.display-item.citation.isi??? 7
social impact