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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Neolignans isolated from Nectandra leucantha induce apoptosis in melanoma cells by disturbance in mitochondrial integrity and redox homeostasis

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de Sousa, Fernanda S. ; Grecco, Simone S. ; Girola, Natalia ; Azevedo, Ricardo A. ; Figueiredo, Carlos R. ; Lago, Joao Henrique G.
Total Authors: 6
Document type: Journal article
Source: Phytochemistry; v. 140, p. 108-117, AUG 2017.
Web of Science Citations: 8

Six neolignans including three previously undescribed metabolites: 1-{[}(7R)-hydroxy-8-propeny1]-3-{[}3'-methoxy-1'-(8'-propeny1)-phenoxy]- 4,5-dimethoxybenzene, 4-hydroxy-5-methoxy-3-{[}3'-methoxy-1'-(8'-propenyl)phenoxyl-1-(7-oxo-8- propenyl)benzene and 4,5-dimethoxy-3-{[}3'-methoxy-1'-(8'-propenyl)phenoxy]-1-(7-oxo-8-propen yl)benzene were isolated from twigs of Nectandra leucantha Nees \& Mart (Lauraceae) using bioactivity-guided fractionation. Cytotoxic activity of isolated compounds was evaluated in vitro against cancer cell lines (SR BR-3, HCT, U87-MG, A2058, and B16F10), being dehy-drodieugenol B and 4-hydroxy-5-methoxy-3-{[}3'-methoxy-1'-(8'-propenyl)phenoxy]-1-(7-oxo-8- propenyl)benzene the most active metabolites. These compounds displayed IC50 values of 78.8 +/- 2.8 and 82.2 +/- 3.5 mu M, respectively, against murine melanoma. Different in vitro mechanism of induced cytotoxicity for this cell line is proposed for both compounds. Obtained results indicated a remarkable effect during the induction of morphological, biochemical and enzymatic features of apoptosis, such as disruption of mitochondrial membrane potential (Delta Psi m), exposure of phosphatidylserine in the outer cell membrane, and-genomic DNA condensation and fragmentation. Dehydrodieugenol B induced caspase-3 and PARP activation and 4-hydroxy-5-methoxy-3-{[}3'-methoxy-1'-(8'-propenyl)phenoxy]-1-(7-oxo-8- propenyl)benzene downregulated the levels of Bcl-2 protein. These effects were accompanied by increased levels of reactive oxygen species as a consequence of mitochondrial damage, followed by F-actin aggregation during the cell death process. Dehydrodieugenol B showed oxidative properties and both compounds, especially 4-hydroxy-5-methoxy-3-{[}3'-methoxy-1'-(8'-propenyl)phenoxyl-1-(7-oxo-8- propenyl)benzene, displayed potential to alkylate nucleophiles, suggesting an accessory mechanism of tumor-induced cytotoxicity by these metabolites. (C) 2017 Elsevier Ltd. All rights reserved. (AU)

FAPESP's process: 15/11936-2 - Use of chemodiversity of plant species in remaining areas of Atlantic Forest from São Paulo State in the selection of biologically active prototypes
Grantee:João Henrique Ghilardi Lago
Support type: Regular Research Grants
FAPESP's process: 15/04143-6 - Naturals and semisynthetics metabolites from twigs of Nectandra leucantha Ness & Mart. (Lauraceae): molecular characterization, potential evaluation and mechanism antitumoral against melanoma
Grantee:Fernanda Samara de Sousa
Support type: Scholarships in Brazil - Doctorate (Direct)