Please use this identifier to cite or link to this item: https://hdl.handle.net/10316/105269
Title: Cytotoxic Mechanism of Sphaerodactylomelol, an Uncommon Bromoditerpene Isolated from Sphaerococcus coronopifolius
Authors: Alves, Celso 
Silva, Joana
Pinteus, Susete
Alonso, Eva
Alvariño, Rebeca
Duarte, Adriana 
Marmitt, Diorge
Goettert, Márcia Inês
Gaspar, Helena 
Alfonso, Amparo
Alpoim, Maria C. 
Botana, Luis M.
Pedrosa, Rui
Keywords: breast cancer; red algae; oxidative stress; marine natural products; apoptosis; DNA damage; biological activities; MCF-7 cells
Issue Date: 4-Mar-2021
Publisher: MDPI
Project: UID/MAR/04292/2020 
UIDP/Multi/04046/2020 
UIDB/04046/2020 
SAICTPAC/0019/ 2015-LISBOA- 01-0145-FEDER-016405 
PTDC/BIA-OUT/29250/2017 
POCI-01-0145-FEDER-029250 
SFRH/BD/103255/2014 
Serial title, monograph or event: Molecules
Volume: 26
Issue: 5
Abstract: Marine natural products have exhibited uncommon chemical structures with relevant antitumor properties highlighting their potential to inspire the development of new anticancer agents. The goal of this work was to study the antitumor activities of the brominated diterpene sphaerodactylomelol, a rare example of the dactylomelane family. Cytotoxicity (10-100 µM; 24 h) was evaluated on tumor cells (A549, CACO-2, HCT-15, MCF-7, NCI-H226, PC-3, SH-SY5Y, SK-ML-28) and the effects estimated by MTT assay. Hydrogen peroxide (H2O2) levels and apoptosis biomarkers (membrane translocation of phosphatidylserine, depolarization of mitochondrial membrane potential, Caspase-9 activity, and DNA condensation and/or fragmentation) were studied in the breast adenocarcinoma cellular model (MCF-7) and its genotoxicity on mouse fibroblasts (L929). Sphaerodactylomelol displayed an IC50 range between 33.04 and 89.41 µM without selective activity for a specific tumor tissue. The cells' viability decrease was accompanied by an increase on H2O2 production, a depolarization of mitochondrial membrane potential and an increase of Caspase-9 activity and DNA fragmentation. However, the DNA damage studies in L929 non-malignant cell line suggested that this compound is not genotoxic for normal fibroblasts. Overall, the results suggest that the cytotoxicity of sphaerodactylomelol seems to be mediated by an increase of H2O2 levels and downstream apoptosis.
URI: https://hdl.handle.net/10316/105269
ISSN: 1420-3049
DOI: 10.3390/molecules26051374
Rights: openAccess
Appears in Collections:I&D CNC - Artigos em Revistas Internacionais

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