Marine Seagrass Extract of <i>Thalassia testudinum</i> Suppresses Colorectal Tumor Growth, Motility and Angiogenesis by Autophagic Stress and Immunogenic Cell Death Pathways
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
Affiliations
Ivones Hernández-Balmaseda
Instituto de Ciencias del Mar (ICIMAR), Calle Loma #14 e/35 y 37, Alturas del Vedado, Plaza de la Revolución, Havana 10400, Cuba
Idania Rodeiro Guerra
Instituto de Ciencias del Mar (ICIMAR), Calle Loma #14 e/35 y 37, Alturas del Vedado, Plaza de la Revolución, Havana 10400, Cuba
Ken Declerck
Laboratory 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, Belgium
José Alfredo Herrera Isidrón
Instituto de Ciencia y Tecnología de Materiales (IMRE), Universidad de la Habana, Zapata y G, Vedado, Plaza de la Revolución, Havana 10400, Cuba
Claudina Pérez-Novo
Laboratory 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, Belgium
Guy Van Camp
Center of Medical Genetics, University of Antwerp and Antwerp University Hospital, Prins Boudewijnlaan 43, 2650 Edegem, Belgium
Olivier De Wever
Laboratory of Experimental Cancer Research, Department of Radiation Oncology and Experimental Cancer Research, Cancer Research Institute Ghent (CRIG), UZ-Gent, 9000 Gent, Belgium
Kethia González
Instituto de Ciencias del Mar (ICIMAR), Calle Loma #14 e/35 y 37, Alturas del Vedado, Plaza de la Revolución, Havana 10400, Cuba
Mayrel Labrada
Center of Molecular Immunology, Calle 17, Atabey, Playa, Havana 11300, Cuba
Adriana Carr
Center of Molecular Immunology, Calle 17, Atabey, Playa, Havana 11300, Cuba
Geovanni Dantas-Cassali
Institute of Biological Sciences (ICB), Federal University of Minas Gerais (UFMG), Belo Horizonte 31207-901, Brazil
Diego Carlos dos Reis
Institute of Biological Sciences (ICB), Federal University of Minas Gerais (UFMG), Belo Horizonte 31207-901, Brazil
Livan Delgado-Roche
Instituto de Ciencias del Mar (ICIMAR), Calle Loma #14 e/35 y 37, Alturas del Vedado, Plaza de la Revolución, Havana 10400, Cuba
Roberto Rafael Nuñez
Instituto de Ciencias del Mar (ICIMAR), Calle Loma #14 e/35 y 37, Alturas del Vedado, Plaza de la Revolución, Havana 10400, Cuba
René Delgado-Hernández
Instituto de Farmacia y Alimentos (IFAL), Universidad de La Habana, (UH), Ave. 23 # 21425 Entre 214 and 222, La Coronela, La Lisa, Havana 13600, Cuba
Miguel David Fernández
Instituto de Ciencias del Mar (ICIMAR), Calle Loma #14 e/35 y 37, Alturas del Vedado, Plaza de la Revolución, Havana 10400, Cuba
Miriam T. Paz-Lopes
Institute of Biological Sciences (ICB), Federal University of Minas Gerais (UFMG), Belo Horizonte 31207-901, Brazil
Wim Vanden Berghe
Laboratory 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, Belgium
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 Thalassia testudinum (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 IC50 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.
