RT Journal Article
T1 Cytotoxic Mechanism of Sphaerodactylomelol, an Uncommon Bromoditerpene Isolated from Sphaerococcus coronopifolius
A1 Alves, Celso
A1 Silva, Joana M.
A1 Pinteus, Susete
A1 Alonso López, Eva
A1 Alvariño Romero, Rebeca
A1 Duarte, Adriana
A1 Marmitt, Diorge
A1 Goettert, Márcia Inês
A1 Gaspar, Helena
A1 Alfonso Rancaño, María Amparo
A1 Alpoim, Maria C.
A1 Botana López, Luis Miguel
A1 Pedrosa, Rui
K1 Breast cancer
K1 Red algae
K1 Oxidative stress
K1 Marine natural products
K1 Apoptosis
K1 DNA damage
K1 Biological activities
K1 MCF-7 cells
AB 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
PB MDPI
YR 2021
FD 2021
LK http://hdl.handle.net/10347/24729
UL http://hdl.handle.net/10347/24729
LA eng
NO Molecules 2021, 26(5), 1374; https://doi.org/10.3390/molecules26051374
NO This work was supported by the Portuguese Foundation for Science and Technology (FCT) through the strategic project UID/MAR/04292/2020 to MARE—Marine and Environmental Sciences Centre and UIDP/Multi/04046/2020 and UIDB/04046/2020 granted to BioISI—BioSystems and Integrative Sciences Institute, through POINT4PAC project (Oncologia de Precisão: Terapias e Tecnologias Inovadoras (SAICTPAC/0019/ 2015-LISBOA- 01-0145-FEDER-016405), through CROSS-ATLANTIC project (PTDC/BIA-OUT/29250/2017), co-financed by COMPETE (POCI-01-0145-FEDER-029250). FCT is also acknowledged for the grant attributed to J.S. (SFRH/BD/103255/2014)
DS Minerva
RD 22 abr 2026