Cytotoxic Mechanism of Sphaerodactylomelol, an Uncommon Bromoditerpene Isolated from Sphaerococcus coronopifolius
Autor(a) principal: | |
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Data de Publicação: | 2021 |
Outros Autores: | , , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10316/105269 https://doi.org/10.3390/molecules26051374 |
Resumo: | 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. |
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Cytotoxic Mechanism of Sphaerodactylomelol, an Uncommon Bromoditerpene Isolated from Sphaerococcus coronopifoliusbreast cancerred algaeoxidative stressmarine natural productsapoptosisDNA damagebiological activitiesMCF-7 cellsAnimalsAntineoplastic AgentsBreast NeoplasmsCell ProliferationCells, CulturedDNA DamageDiterpenesFemaleFibroblastsHumansHydrogen PeroxideMembrane Potential, MitochondrialMiceRhodophytaApoptosisMarine 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.MDPI2021-03-04info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://hdl.handle.net/10316/105269http://hdl.handle.net/10316/105269https://doi.org/10.3390/molecules26051374eng1420-3049Alves, CelsoSilva, JoanaPinteus, SuseteAlonso, EvaAlvariño, RebecaDuarte, AdrianaMarmitt, DiorgeGoettert, Márcia InêsGaspar, HelenaAlfonso, AmparoAlpoim, Maria C.Botana, Luis M.Pedrosa, Ruiinfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-02-13T12:41:16Zoai:estudogeral.uc.pt:10316/105269Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T21:21:52.014648Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Cytotoxic Mechanism of Sphaerodactylomelol, an Uncommon Bromoditerpene Isolated from Sphaerococcus coronopifolius |
title |
Cytotoxic Mechanism of Sphaerodactylomelol, an Uncommon Bromoditerpene Isolated from Sphaerococcus coronopifolius |
spellingShingle |
Cytotoxic Mechanism of Sphaerodactylomelol, an Uncommon Bromoditerpene Isolated from Sphaerococcus coronopifolius Alves, Celso breast cancer red algae oxidative stress marine natural products apoptosis DNA damage biological activities MCF-7 cells Animals Antineoplastic Agents Breast Neoplasms Cell Proliferation Cells, Cultured DNA Damage Diterpenes Female Fibroblasts Humans Hydrogen Peroxide Membrane Potential, Mitochondrial Mice Rhodophyta Apoptosis |
title_short |
Cytotoxic Mechanism of Sphaerodactylomelol, an Uncommon Bromoditerpene Isolated from Sphaerococcus coronopifolius |
title_full |
Cytotoxic Mechanism of Sphaerodactylomelol, an Uncommon Bromoditerpene Isolated from Sphaerococcus coronopifolius |
title_fullStr |
Cytotoxic Mechanism of Sphaerodactylomelol, an Uncommon Bromoditerpene Isolated from Sphaerococcus coronopifolius |
title_full_unstemmed |
Cytotoxic Mechanism of Sphaerodactylomelol, an Uncommon Bromoditerpene Isolated from Sphaerococcus coronopifolius |
title_sort |
Cytotoxic Mechanism of Sphaerodactylomelol, an Uncommon Bromoditerpene Isolated from Sphaerococcus coronopifolius |
author |
Alves, Celso |
author_facet |
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 |
author_role |
author |
author2 |
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 |
author2_role |
author author author author author author author author author author author author |
dc.contributor.author.fl_str_mv |
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 |
dc.subject.por.fl_str_mv |
breast cancer red algae oxidative stress marine natural products apoptosis DNA damage biological activities MCF-7 cells Animals Antineoplastic Agents Breast Neoplasms Cell Proliferation Cells, Cultured DNA Damage Diterpenes Female Fibroblasts Humans Hydrogen Peroxide Membrane Potential, Mitochondrial Mice Rhodophyta Apoptosis |
topic |
breast cancer red algae oxidative stress marine natural products apoptosis DNA damage biological activities MCF-7 cells Animals Antineoplastic Agents Breast Neoplasms Cell Proliferation Cells, Cultured DNA Damage Diterpenes Female Fibroblasts Humans Hydrogen Peroxide Membrane Potential, Mitochondrial Mice Rhodophyta Apoptosis |
description |
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. |
publishDate |
2021 |
dc.date.none.fl_str_mv |
2021-03-04 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10316/105269 http://hdl.handle.net/10316/105269 https://doi.org/10.3390/molecules26051374 |
url |
http://hdl.handle.net/10316/105269 https://doi.org/10.3390/molecules26051374 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
1420-3049 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.publisher.none.fl_str_mv |
MDPI |
publisher.none.fl_str_mv |
MDPI |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
institution |
RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
collection |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository.name.fl_str_mv |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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1799134109413408768 |