Marine Seagrass Extract of <i>Thalassia testudinum</i> Suppresses Colorectal Tumor Growth, Motility and Angiogenesis by Autophagic Stress and Immunogenic Cell Death Pathways

Marine plants have become an inexhaustible reservoir of new phytopharmaceuticals for cancer treatment. We demonstrate in vitro/in vivo antitumor efficacy of a standardized polyphenol extract from the marine angiosperm <i>Thalassia testudinum</i> (TTE) in colon tumor cell lines (RKO, SW48...

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Main Authors: Ivones Hernández-Balmaseda, Idania Rodeiro Guerra, Ken Declerck, José Alfredo Herrera Isidrón, Claudina Pérez-Novo, Guy Van Camp, Olivier De Wever, Kethia González, Mayrel Labrada, Adriana Carr, Geovanni Dantas-Cassali, Diego Carlos dos Reis, Livan Delgado-Roche, Roberto Rafael Nuñez, René Delgado-Hernández, Miguel David Fernández, Miriam T. Paz-Lopes, Wim Vanden Berghe
Format: Article
Language:English
Published: MDPI AG 2021-01-01
Series:Marine Drugs
Subjects:
Online Access:https://www.mdpi.com/1660-3397/19/2/52
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author Ivones Hernández-Balmaseda
Idania Rodeiro Guerra
Ken Declerck
José Alfredo Herrera Isidrón
Claudina Pérez-Novo
Guy Van Camp
Olivier De Wever
Kethia González
Mayrel Labrada
Adriana Carr
Geovanni Dantas-Cassali
Diego Carlos dos Reis
Livan Delgado-Roche
Roberto Rafael Nuñez
René Delgado-Hernández
Miguel David Fernández
Miriam T. Paz-Lopes
Wim Vanden Berghe
author_facet Ivones Hernández-Balmaseda
Idania Rodeiro Guerra
Ken Declerck
José Alfredo Herrera Isidrón
Claudina Pérez-Novo
Guy Van Camp
Olivier De Wever
Kethia González
Mayrel Labrada
Adriana Carr
Geovanni Dantas-Cassali
Diego Carlos dos Reis
Livan Delgado-Roche
Roberto Rafael Nuñez
René Delgado-Hernández
Miguel David Fernández
Miriam T. Paz-Lopes
Wim Vanden Berghe
author_sort Ivones Hernández-Balmaseda
collection DOAJ
description Marine plants have become an inexhaustible reservoir of new phytopharmaceuticals for cancer treatment. We demonstrate in vitro/in vivo antitumor efficacy of a standardized polyphenol extract from the marine angiosperm <i>Thalassia testudinum</i> (TTE) in colon tumor cell lines (RKO, SW480, and CT26) and a syngeneic allograft murine colorectal cancer model. MTT assays revealed a dose-dependent decrease of cell viability of RKO, CT26, and SW480 cells upon TTE treatment with IC<sub>50</sub> values of, respectively, 175, 115, and 60 μg/mL. Furthermore, TTE significantly prevented basal and bFGF-induced angiogenesis in the chicken chorioallantoic membrane angiogenesis assay. In addition, TTE suppressed bFGF-induced migration of endothelial cells in a wound closure assay. Finally, TTE treatment abrogated CT26 colorectal cancer growth and increased overall organism survival in a syngeneic murine allograft model. Corresponding transcriptome profiling and pathway analysis allowed for the identification of the mechanism of action for the antitumor effects of TTE. In line with our in vitro/in vivo results, TTE treatment triggers ATF4-P53-NFκB specific gene expression and autophagy stress pathways. This results in suppression of colon cancer cell growth, cell motility, and angiogenesis pathways in vitro and in addition promotes antitumor immunogenic cell death in vivo.
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spelling doaj.art-9e8ac325380a4609b27730226ac959bd2023-12-03T14:16:30ZengMDPI AGMarine Drugs1660-33972021-01-011925210.3390/md19020052Marine Seagrass Extract of <i>Thalassia testudinum</i> Suppresses Colorectal Tumor Growth, Motility and Angiogenesis by Autophagic Stress and Immunogenic Cell Death PathwaysIvones Hernández-Balmaseda0Idania Rodeiro Guerra1Ken Declerck2José Alfredo Herrera Isidrón3Claudina Pérez-Novo4Guy Van Camp5Olivier De Wever6Kethia González7Mayrel Labrada8Adriana Carr9Geovanni Dantas-Cassali10Diego Carlos dos Reis11Livan Delgado-Roche12Roberto Rafael Nuñez13René Delgado-Hernández14Miguel David Fernández15Miriam T. Paz-Lopes16Wim Vanden Berghe17Instituto de Ciencias del Mar (ICIMAR), Calle Loma #14 e/35 y 37, Alturas del Vedado, Plaza de la Revolución, Havana 10400, CubaInstituto de Ciencias del Mar (ICIMAR), Calle Loma #14 e/35 y 37, Alturas del Vedado, Plaza de la Revolución, Havana 10400, CubaLaboratory of Protein Science, Proteomics and Epigenetic Signaling (PPES) and Integrated Personalized and Precision Oncology Network (IPPON), Department of Biomedical Sciences, Campus Drie Eiken, University of Antwerp, Building S, 4th Floor, Universiteitsplein 1, 2610 Wilrijk, BelgiumInstituto de Ciencia y Tecnología de Materiales (IMRE), Universidad de la Habana, Zapata y G, Vedado, Plaza de la Revolución, Havana 10400, CubaLaboratory of Protein Science, Proteomics and Epigenetic Signaling (PPES) and Integrated Personalized and Precision Oncology Network (IPPON), Department of Biomedical Sciences, Campus Drie Eiken, University of Antwerp, Building S, 4th Floor, Universiteitsplein 1, 2610 Wilrijk, BelgiumCenter of Medical Genetics, University of Antwerp and Antwerp University Hospital, Prins Boudewijnlaan 43, 2650 Edegem, BelgiumLaboratory of Experimental Cancer Research, Department of Radiation Oncology and Experimental Cancer Research, Cancer Research Institute Ghent (CRIG), UZ-Gent, 9000 Gent, BelgiumInstituto de Ciencias del Mar (ICIMAR), Calle Loma #14 e/35 y 37, Alturas del Vedado, Plaza de la Revolución, Havana 10400, CubaCenter of Molecular Immunology, Calle 17, Atabey, Playa, Havana 11300, CubaCenter of Molecular Immunology, Calle 17, Atabey, Playa, Havana 11300, CubaInstitute of Biological Sciences (ICB), Federal University of Minas Gerais (UFMG), Belo Horizonte 31207-901, BrazilInstitute of Biological Sciences (ICB), Federal University of Minas Gerais (UFMG), Belo Horizonte 31207-901, BrazilInstituto de Ciencias del Mar (ICIMAR), Calle Loma #14 e/35 y 37, Alturas del Vedado, Plaza de la Revolución, Havana 10400, CubaInstituto de Ciencias del Mar (ICIMAR), Calle Loma #14 e/35 y 37, Alturas del Vedado, Plaza de la Revolución, Havana 10400, CubaInstituto de Farmacia y Alimentos (IFAL), Universidad de La Habana, (UH), Ave. 23 # 21425 Entre 214 and 222, La Coronela, La Lisa, Havana 13600, CubaInstituto de Ciencias del Mar (ICIMAR), Calle Loma #14 e/35 y 37, Alturas del Vedado, Plaza de la Revolución, Havana 10400, CubaInstitute of Biological Sciences (ICB), Federal University of Minas Gerais (UFMG), Belo Horizonte 31207-901, BrazilLaboratory of Protein Science, Proteomics and Epigenetic Signaling (PPES) and Integrated Personalized and Precision Oncology Network (IPPON), Department of Biomedical Sciences, Campus Drie Eiken, University of Antwerp, Building S, 4th Floor, Universiteitsplein 1, 2610 Wilrijk, BelgiumMarine plants have become an inexhaustible reservoir of new phytopharmaceuticals for cancer treatment. We demonstrate in vitro/in vivo antitumor efficacy of a standardized polyphenol extract from the marine angiosperm <i>Thalassia testudinum</i> (TTE) in colon tumor cell lines (RKO, SW480, and CT26) and a syngeneic allograft murine colorectal cancer model. MTT assays revealed a dose-dependent decrease of cell viability of RKO, CT26, and SW480 cells upon TTE treatment with IC<sub>50</sub> values of, respectively, 175, 115, and 60 μg/mL. Furthermore, TTE significantly prevented basal and bFGF-induced angiogenesis in the chicken chorioallantoic membrane angiogenesis assay. In addition, TTE suppressed bFGF-induced migration of endothelial cells in a wound closure assay. Finally, TTE treatment abrogated CT26 colorectal cancer growth and increased overall organism survival in a syngeneic murine allograft model. Corresponding transcriptome profiling and pathway analysis allowed for the identification of the mechanism of action for the antitumor effects of TTE. In line with our in vitro/in vivo results, TTE treatment triggers ATF4-P53-NFκB specific gene expression and autophagy stress pathways. This results in suppression of colon cancer cell growth, cell motility, and angiogenesis pathways in vitro and in addition promotes antitumor immunogenic cell death in vivo.https://www.mdpi.com/1660-3397/19/2/52<i>Thalassia testudinum</i>cytotoxicityantitumoranti-angiogenicgene expression
spellingShingle Ivones Hernández-Balmaseda
Idania Rodeiro Guerra
Ken Declerck
José Alfredo Herrera Isidrón
Claudina Pérez-Novo
Guy Van Camp
Olivier De Wever
Kethia González
Mayrel Labrada
Adriana Carr
Geovanni Dantas-Cassali
Diego Carlos dos Reis
Livan Delgado-Roche
Roberto Rafael Nuñez
René Delgado-Hernández
Miguel David Fernández
Miriam T. Paz-Lopes
Wim Vanden Berghe
Marine Seagrass Extract of <i>Thalassia testudinum</i> Suppresses Colorectal Tumor Growth, Motility and Angiogenesis by Autophagic Stress and Immunogenic Cell Death Pathways
Marine Drugs
<i>Thalassia testudinum</i>
cytotoxicity
antitumor
anti-angiogenic
gene expression
title Marine Seagrass Extract of <i>Thalassia testudinum</i> Suppresses Colorectal Tumor Growth, Motility and Angiogenesis by Autophagic Stress and Immunogenic Cell Death Pathways
title_full Marine Seagrass Extract of <i>Thalassia testudinum</i> Suppresses Colorectal Tumor Growth, Motility and Angiogenesis by Autophagic Stress and Immunogenic Cell Death Pathways
title_fullStr Marine Seagrass Extract of <i>Thalassia testudinum</i> Suppresses Colorectal Tumor Growth, Motility and Angiogenesis by Autophagic Stress and Immunogenic Cell Death Pathways
title_full_unstemmed Marine Seagrass Extract of <i>Thalassia testudinum</i> Suppresses Colorectal Tumor Growth, Motility and Angiogenesis by Autophagic Stress and Immunogenic Cell Death Pathways
title_short Marine Seagrass Extract of <i>Thalassia testudinum</i> Suppresses Colorectal Tumor Growth, Motility and Angiogenesis by Autophagic Stress and Immunogenic Cell Death Pathways
title_sort marine seagrass extract of i thalassia testudinum i suppresses colorectal tumor growth motility and angiogenesis by autophagic stress and immunogenic cell death pathways
topic <i>Thalassia testudinum</i>
cytotoxicity
antitumor
anti-angiogenic
gene expression
url https://www.mdpi.com/1660-3397/19/2/52
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