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

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.

Autoren

Eva María Domínguez-Martín
Mariana Magalhães
Ana María Díaz-Lanza
Mário P Marques
Salvatore Princiotto
Ana M Gómez
Thomas Efferth
Célia Cabral
Patricia Rijo

DOI

10.3390/molecules27123813

eISSN

1420-3049

Ausgabe der Veröffentlichung

12

Zeitschrift

Molecules

Sprache

en

Online publication date

2022

Paginierung

3813 - 3813

Status

Published online

Herausgeber

MDPI AG

Herausgeber URL

http://dx.doi.org/10.3390/molecules27123813

Datum der Datenerfassung

2022

Titel

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

Ausgabe der Zeitschrift

27

Data source: Crossref

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.

Addresses

Center for Research in Biosciences & Health Technologies (CBIOS), Universidade Lusófona de Humanidades e Tecnologias, Campo Grande 376, 1749-024 Lisbon, Portugal.

Autoren

Eva María Domínguez-Martín
Mariana Magalhães
Ana María Díaz-Lanza
Mário P Marques
Salvatore Princiotto
Ana M Gómez
Thomas Efferth
Célia Cabral
Patricia Rijo

DOI

10.3390/molecules27123813

eISSN

1420-3049

Externe Identifier

PubMed Identifier: 35744938
PubMed Central ID: PMC9230782

Funding acknowledgements

Fundação para a Ciência e Tecnologia: PEst-OE/SAU/UI4013/2014, UID/DTP/04567/2016, UIDB/04567/2020, UIDP/04567/2020, UIDB/04539/2020, UIDP/04539/2020
ILIND: RTI2018-094862-B-100
ILIND: COFAC/ILIND/CBIOS/1/2020
Spanish Ministerio de Ciencia e Innovación: RTI2018-094862-B-100

Open access

true

ISSN

1420-3049

Ausgabe der Veröffentlichung

12

Zeitschrift

Molecules (Basel, Switzerland)

Schlüsselwörter

Humans
Plectranthus
Brain Neoplasms
Plant Extracts
Tissue Distribution
Phytochemicals
Abietanes

Sprache

eng

Medium

Electronic

Online publication date

2022

Open access status

Open Access

Paginierung

3813

Datum der Veröffentlichung

2022

Status

Published

Publisher licence

CC BY

Datum der Datenerfassung

2022

Titel

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

Sub types

research-article
Journal Article

Ausgabe der Zeitschrift

27

Files

https://www.mdpi.com/1420-3049/27/12/3813/pdf?version=1655710949 https://europepmc.org/articles/PMC9230782?pdf=render

Data source: Europe PubMed Central

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.

Date of acceptance

2022

Autoren

Eva María Domínguez-Martín
Mariana Magalhães
Ana María Díaz-Lanza
Mário P Marques
Salvatore Princiotto
Ana M Gómez
Thomas Efferth
Célia Cabral
Patricia Rijo

Autoren-URL

https://www.ncbi.nlm.nih.gov/pubmed/35744938

DOI

10.3390/molecules27123813

eISSN

1420-3049

Externe Identifier

PubMed Central ID: PMC9230782

Funding acknowledgements

Fundação para a Ciência e Tecnologia: PEst-OE/SAU/UI4013/2014, UID/DTP/04567/2016, UIDB/04567/2020, UIDP/04567/2020, UIDB/04539/2020, UIDP/04539/2020
ILIND: COFAC/ILIND/CBIOS/1/2020
Spanish Ministerio de Ciencia e Innovación: RTI2018-094862-B-100

Ausgabe der Veröffentlichung

12

Zeitschrift

Molecules

Schlüsselwörter

Lamiaceae
Plectranthus
cancer
diterpenes
glioblastoma
phytochemical
royleanones
Abietanes
Brain Neoplasms
Humans
Phytochemicals
Plant Extracts
Plectranthus
Tissue Distribution

Sprache

eng

Country

Switzerland

PII

molecules27123813

Datum der Veröffentlichung

2022

Status

Published online

Datum, an dem der Datensatz öffentlich gemacht wurde

2022

Titel

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

Sub types

Journal Article

Ausgabe der Zeitschrift

27

Data source: PubMed

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

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