Disclosing the antitumour potential of the marine bromoditerpene sphaerococcenol A on distinct cancer cellular models
Autor(a) principal: | |
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Data de Publicação: | 2022 |
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/10316/100508 https://doi.org/10.1016/j.biopha.2022.112886 |
Resumo: | Nature has revealed to be a key source of innovative anticancer drugs. This study evaluated the antitumour potential of the marine bromoditerpene sphaerococcenol A on different cancer cellular models. Dose-response analyses (0.1-100 µM; 24 h) were accomplished in eight different tumour cell lines (A549, CACO-2, HCT-15, MCF-7, NCI-H226, PC-3, SH-SY5Y, SK-MEL-28). Deeper studies were conducted on MFC-7 cells, namely, determination of hydrogen peroxide (H2O2) levels and evaluation of apoptosis biomarkers (phosphatidylserine membrane translocation, mitochondrial dysfunction, Caspase-9 activity, and DNA changes). The ability of the compound to induce genotoxicity was verified in L929 fibroblasts. Sphaerococcenol A capacity to impact colorectal-cancer stem cells (CSCs) tumourspheres (HT29, HCT116, SW620) was evaluated by determining tumourspheres viability, number, and area, as well as the proteasome inhibitory activity. Sphaerococcenol A hepatoxicity was studied in AML12 hepatocytes. The compound exhibited cytotoxicity in all malignant cell lines (IC50 ranging from 4.5 to 16.6 µM). MCF-7 cells viability loss was accompanied by H2O2 generation, mitochondrial dysfunction, Caspase-9 activation and DNA nuclear morphology changes. Furthermore, the compound displayed the lowest IC50 on HT29-derived tumourspheres (0.70 µM), followed by HCT116 (1.77 µM) and SW620 (2.74 µM), impacting the HT29 tumoursphere formation by reducing their number and area. Finally, the compound displayed low cytotoxicity on AML12 hepatocytes without genotoxicity. Overall, sphaerococcenol A exhibits broad cytotoxic effects on different tumour cells, increasing H2O2 production and apoptosis. It also affects colorectal CSCs-enriched tumoursphere development. These data highlight the relevance to include sphaerococcenol A in further pharmacological studies aiming cancer treatments. |
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Disclosing the antitumour potential of the marine bromoditerpene sphaerococcenol A on distinct cancer cellular modelsAlgaeMarine natural productsApoptosisOxidative stressProteasomeCancer stem cellsApoptosisCaco-2 CellsCaspase 9Cell Line, TumorDNADiterpenesHumansHydrogen PeroxideAntineoplastic AgentsColorectal NeoplasmsNature has revealed to be a key source of innovative anticancer drugs. This study evaluated the antitumour potential of the marine bromoditerpene sphaerococcenol A on different cancer cellular models. Dose-response analyses (0.1-100 µM; 24 h) were accomplished in eight different tumour cell lines (A549, CACO-2, HCT-15, MCF-7, NCI-H226, PC-3, SH-SY5Y, SK-MEL-28). Deeper studies were conducted on MFC-7 cells, namely, determination of hydrogen peroxide (H2O2) levels and evaluation of apoptosis biomarkers (phosphatidylserine membrane translocation, mitochondrial dysfunction, Caspase-9 activity, and DNA changes). The ability of the compound to induce genotoxicity was verified in L929 fibroblasts. Sphaerococcenol A capacity to impact colorectal-cancer stem cells (CSCs) tumourspheres (HT29, HCT116, SW620) was evaluated by determining tumourspheres viability, number, and area, as well as the proteasome inhibitory activity. Sphaerococcenol A hepatoxicity was studied in AML12 hepatocytes. The compound exhibited cytotoxicity in all malignant cell lines (IC50 ranging from 4.5 to 16.6 µM). MCF-7 cells viability loss was accompanied by H2O2 generation, mitochondrial dysfunction, Caspase-9 activation and DNA nuclear morphology changes. Furthermore, the compound displayed the lowest IC50 on HT29-derived tumourspheres (0.70 µM), followed by HCT116 (1.77 µM) and SW620 (2.74 µM), impacting the HT29 tumoursphere formation by reducing their number and area. Finally, the compound displayed low cytotoxicity on AML12 hepatocytes without genotoxicity. Overall, sphaerococcenol A exhibits broad cytotoxic effects on different tumour cells, increasing H2O2 production and apoptosis. It also affects colorectal CSCs-enriched tumoursphere development. These data highlight the relevance to include sphaerococcenol A in further pharmacological studies aiming cancer treatments.2022-05info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://hdl.handle.net/10316/100508http://hdl.handle.net/10316/100508https://doi.org/10.1016/j.biopha.2022.112886eng07533322Alves, CelsoSilva, JoanaAfonso, Marta BGuedes, Romina A.Guedes, Rita C.Alvariño, RebecaPinteus, SuseteGaspar, HelenaGoettert, Márcia I.Alfonso, AmparoRodrigues, Cecília M. P.Alpoím, Maria C.Botana, LuisPedrosa, 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:RCAAP2022-06-27T20:34:27Zoai:estudogeral.uc.pt:10316/100508Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T21:17:52.917284Repositório 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 |
Disclosing the antitumour potential of the marine bromoditerpene sphaerococcenol A on distinct cancer cellular models |
title |
Disclosing the antitumour potential of the marine bromoditerpene sphaerococcenol A on distinct cancer cellular models |
spellingShingle |
Disclosing the antitumour potential of the marine bromoditerpene sphaerococcenol A on distinct cancer cellular models Alves, Celso Algae Marine natural products Apoptosis Oxidative stress Proteasome Cancer stem cells Apoptosis Caco-2 Cells Caspase 9 Cell Line, Tumor DNA Diterpenes Humans Hydrogen Peroxide Antineoplastic Agents Colorectal Neoplasms |
title_short |
Disclosing the antitumour potential of the marine bromoditerpene sphaerococcenol A on distinct cancer cellular models |
title_full |
Disclosing the antitumour potential of the marine bromoditerpene sphaerococcenol A on distinct cancer cellular models |
title_fullStr |
Disclosing the antitumour potential of the marine bromoditerpene sphaerococcenol A on distinct cancer cellular models |
title_full_unstemmed |
Disclosing the antitumour potential of the marine bromoditerpene sphaerococcenol A on distinct cancer cellular models |
title_sort |
Disclosing the antitumour potential of the marine bromoditerpene sphaerococcenol A on distinct cancer cellular models |
author |
Alves, Celso |
author_facet |
Alves, Celso Silva, Joana Afonso, Marta B Guedes, Romina A. Guedes, Rita C. Alvariño, Rebeca Pinteus, Susete Gaspar, Helena Goettert, Márcia I. Alfonso, Amparo Rodrigues, Cecília M. P. Alpoím, Maria C. Botana, Luis Pedrosa, Rui |
author_role |
author |
author2 |
Silva, Joana Afonso, Marta B Guedes, Romina A. Guedes, Rita C. Alvariño, Rebeca Pinteus, Susete Gaspar, Helena Goettert, Márcia I. Alfonso, Amparo Rodrigues, Cecília M. P. Alpoím, Maria C. Botana, Luis Pedrosa, Rui |
author2_role |
author author author author author author author author author author author author author |
dc.contributor.author.fl_str_mv |
Alves, Celso Silva, Joana Afonso, Marta B Guedes, Romina A. Guedes, Rita C. Alvariño, Rebeca Pinteus, Susete Gaspar, Helena Goettert, Márcia I. Alfonso, Amparo Rodrigues, Cecília M. P. Alpoím, Maria C. Botana, Luis Pedrosa, Rui |
dc.subject.por.fl_str_mv |
Algae Marine natural products Apoptosis Oxidative stress Proteasome Cancer stem cells Apoptosis Caco-2 Cells Caspase 9 Cell Line, Tumor DNA Diterpenes Humans Hydrogen Peroxide Antineoplastic Agents Colorectal Neoplasms |
topic |
Algae Marine natural products Apoptosis Oxidative stress Proteasome Cancer stem cells Apoptosis Caco-2 Cells Caspase 9 Cell Line, Tumor DNA Diterpenes Humans Hydrogen Peroxide Antineoplastic Agents Colorectal Neoplasms |
description |
Nature has revealed to be a key source of innovative anticancer drugs. This study evaluated the antitumour potential of the marine bromoditerpene sphaerococcenol A on different cancer cellular models. Dose-response analyses (0.1-100 µM; 24 h) were accomplished in eight different tumour cell lines (A549, CACO-2, HCT-15, MCF-7, NCI-H226, PC-3, SH-SY5Y, SK-MEL-28). Deeper studies were conducted on MFC-7 cells, namely, determination of hydrogen peroxide (H2O2) levels and evaluation of apoptosis biomarkers (phosphatidylserine membrane translocation, mitochondrial dysfunction, Caspase-9 activity, and DNA changes). The ability of the compound to induce genotoxicity was verified in L929 fibroblasts. Sphaerococcenol A capacity to impact colorectal-cancer stem cells (CSCs) tumourspheres (HT29, HCT116, SW620) was evaluated by determining tumourspheres viability, number, and area, as well as the proteasome inhibitory activity. Sphaerococcenol A hepatoxicity was studied in AML12 hepatocytes. The compound exhibited cytotoxicity in all malignant cell lines (IC50 ranging from 4.5 to 16.6 µM). MCF-7 cells viability loss was accompanied by H2O2 generation, mitochondrial dysfunction, Caspase-9 activation and DNA nuclear morphology changes. Furthermore, the compound displayed the lowest IC50 on HT29-derived tumourspheres (0.70 µM), followed by HCT116 (1.77 µM) and SW620 (2.74 µM), impacting the HT29 tumoursphere formation by reducing their number and area. Finally, the compound displayed low cytotoxicity on AML12 hepatocytes without genotoxicity. Overall, sphaerococcenol A exhibits broad cytotoxic effects on different tumour cells, increasing H2O2 production and apoptosis. It also affects colorectal CSCs-enriched tumoursphere development. These data highlight the relevance to include sphaerococcenol A in further pharmacological studies aiming cancer treatments. |
publishDate |
2022 |
dc.date.none.fl_str_mv |
2022-05 |
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/10316/100508 http://hdl.handle.net/10316/100508 https://doi.org/10.1016/j.biopha.2022.112886 |
url |
http://hdl.handle.net/10316/100508 https://doi.org/10.1016/j.biopha.2022.112886 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
07533322 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
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 |
instacron_str |
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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1799134074302889984 |