Cytotoxic mechanism of sphaerodactylomelol, an uncommon bromoditerpene isolated from sphaerococcus coronopifolius

Autor: Luis M. Botana, Joana Silva, Adriana Yumi Sato Duarte, Helena Gaspar, M. C. Alpoim, Celso Alves, Rebeca Alvariño, Amparo Alfonso, Susete Pinteus, Eva Alonso, Diorge Jônatas Marmitt, Márcia Inês Goettert, Rui Pedrosa
Přispěvatelé: Universidade de Santiago de Compostela. Departamento de Farmacoloxía, Farmacia e Tecnoloxía Farmacéutica
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Pharmaceutical Science
Apoptosis
medicine.disease_cause
Analytical Chemistry
Mice
0302 clinical medicine
Breast cancer
Drug Discovery
oxidative stress
MCF-7 cells
Cytotoxicity
Cells
Cultured
red algae
Membrane Potential
Mitochondrial
0303 health sciences
Red algae
Chemistry
Biological activities
Depolarization
Chemistry (miscellaneous)
030220 oncology & carcinogenesis
Marine natural products
Molecular Medicine
DNA fragmentation
Female
Diterpenes
DNA damage
Antineoplastic Agents
Breast Neoplasms
Article
lcsh:QD241-441
03 medical and health sciences
breast cancer
lcsh:Organic chemistry
medicine
Animals
Humans
MTT assay
Physical and Theoretical Chemistry
Fragmentation (cell biology)
030304 developmental biology
Cell Proliferation
Organic Chemistry
biological activities
marine natural products
Hydrogen Peroxide
Fibroblasts
Molecular biology
Oxidative stress
Rhodophyta
Genotoxicity
DNA Damage
Zdroj: Minerva: Repositorio Institucional de la Universidad de Santiago de Compostela
Universidad de Santiago de Compostela (USC)
Repositório Científico de Acesso Aberto de Portugal
Repositório Científico de Acesso Aberto de Portugal (RCAAP)
instacron:RCAAP
Molecules
Volume 26
Issue 5
Minerva. Repositorio Institucional de la Universidad de Santiago de Compostela
instname
Molecules, Vol 26, Iss 1374, p 1374 (2021)
Popis: 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.
Databáze: OpenAIRE
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