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Marine seagrass extract of Thalassia testudinum suppresses colorectal tumor growth, motility and angiogenesis by autophagic stress and immunogenic cell death pathways
Hernandez-Balmaseda, I.; Guerra, I.R.; Declerck, K.; Isidron, J.A.H.; Perez-Novo, C.; Van Camp, G.; De Wever, O.; Gonzalez, K.; Labrada, M.; Carr, A.; Dantas-Cassali, G.; dos Reis, D.C.; Delgado-Roche, L.; Nunez, R.R.; Delgado-Hernandez, R.; Fernandez, M.D.; ; Vanden Berghe, W. (2021). Marine seagrass extract of Thalassia testudinum suppresses colorectal tumor growth, motility and angiogenesis by autophagic stress and immunogenic cell death pathways. Mar. Drugs 19(2): 52. https://hdl.handle.net/10.3390/md19020052
In: Marine Drugs. Molecular Diversity Preservation International (MDPI): Basel. ISSN 1660-3397; e-ISSN 1660-3397, meer
Peer reviewed article  

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Trefwoorden
    Thalassia testudinum K.D.Koenig, 1805 [WoRMS]
    Marien/Kust
Author keywords
    Thalassia testudinum; cytotoxicity; antitumor; anti-angiogenic; gene expression

Auteurs  Top 
  • Hernandez-Balmaseda, I.
  • Guerra, I.R.
  • Declerck, K., meer
  • Isidron, J.A.H.
  • Perez-Novo, C.
  • Van Camp, G.
  • De Wever, O.
  • Gonzalez, K.
  • Labrada, M.
  • Carr, A.
  • Dantas-Cassali, G.
  • dos Reis, D.C.
  • Delgado-Roche, L.
  • Nunez, R.R.
  • Delgado-Hernandez, R.
  • Fernandez, M.D.
  • Vanden Berghe, W., meer

Abstract
    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.

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