Polyphenolic Fraction Obtained From Thalassia testudinum Marine Plant and Thalassiolin B Exert Cytotoxic Effects in Colorectal Cancer Cells and Arrest Tumor Progression in a Xenograft Mouse Model

Marine plants are important sources of pharmacologically active metabolites. The aim of the present work was to evaluate the cytotoxic and antitumor activity of a polyphenolic fraction obtained from Thalassia testudinum marine plant and thalassiolin B in human colorectal cancer cells. Human cancer c...

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Main Authors: Livan Delgado-Roche, Kethia González, Fernando Mesta, Beatriz Couder, Zaira Tavarez, Ruby Zavala, Ivones Hernandez, Gabino Garrido, Idania Rodeiro, Wim Vanden Berghe
Format: Article
Language:English
Published: Frontiers Media S.A. 2020-11-01
Series:Frontiers in Pharmacology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fphar.2020.592985/full
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author Livan Delgado-Roche
Livan Delgado-Roche
Kethia González
Fernando Mesta
Beatriz Couder
Zaira Tavarez
Ruby Zavala
Ivones Hernandez
Gabino Garrido
Idania Rodeiro
Wim Vanden Berghe
author_facet Livan Delgado-Roche
Livan Delgado-Roche
Kethia González
Fernando Mesta
Beatriz Couder
Zaira Tavarez
Ruby Zavala
Ivones Hernandez
Gabino Garrido
Idania Rodeiro
Wim Vanden Berghe
author_sort Livan Delgado-Roche
collection DOAJ
description Marine plants are important sources of pharmacologically active metabolites. The aim of the present work was to evaluate the cytotoxic and antitumor activity of a polyphenolic fraction obtained from Thalassia testudinum marine plant and thalassiolin B in human colorectal cancer cells. Human cancer cell lines, including HCT15, HCT116, SW260, and HT29 were treated with tested products for cytotoxicity evaluation by crystal violet assay. The potential proapoptotic effect of these natural products was assessed by flow cytometry in HCT15 cells at 48 h using Annexin V-FITC/propidium iodide. In addition, reactive oxygen species (ROS) generation was measured by fluorescence using DCFH-DA staining, and sulfhydryl concentration by spectrophotometry. The in vivo antitumor activity of the polyphenolic fraction (25 mg/kg) was evaluated in a xenograft model in nu/nu mice. In vivo proapoptotic effect was also evaluated by immunohistochemistry using anti-caspase 3 and anti-Bcl-2 antibodies. The results showed that tested products exert colorectal cancer cell cytotoxicity. Besides, the tested products induced a significant increase (p < 0.05) of intracellular ROS generation, and a depletion of sulfhydryl concentration in HCT15 cells. The polyphenolic fraction arrested tumor growth and induced apoptosis in the xenograft mice model. These results demonstrate the cytotoxic activity of T. testudinum metabolites associated, at least, with ROS overproduction and pro-apoptotic effects. Here we demonstrated for the first time the antitumor activity of a T. testudinum polar extract in a xenograft mice model. These results suggest the potential use of T. testudinum marine plant metabolites as adjuvant treatment in cancer therapy.
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spelling doaj.art-11ef240ae4b0423db23b276f5e8cdb262022-12-21T22:09:19ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122020-11-011110.3389/fphar.2020.592985592985Polyphenolic Fraction Obtained From Thalassia testudinum Marine Plant and Thalassiolin B Exert Cytotoxic Effects in Colorectal Cancer Cells and Arrest Tumor Progression in a Xenograft Mouse ModelLivan Delgado-Roche0Livan Delgado-Roche1Kethia González2Fernando Mesta3Beatriz Couder4Zaira Tavarez5Ruby Zavala6Ivones Hernandez7Gabino Garrido8Idania Rodeiro9Wim Vanden Berghe10Dirección Médica, Laboratorios Liomont S.A. de C.V., Ciudad de México, MéxicoInstituto de Ciencias del Mar (ICIMAR), La Habana, CubaInstituto de Ciencias del Mar (ICIMAR), La Habana, CubaEscuela Nacional de Medicina y Homeopatía, Instituto Politécnico Nacional, Ciudad de México, MéxicoUniversidad Nacional Autónoma de Mexico, Ciudad Universitaria, Ciudad de México, MéxicoUniversidad Nacional Autónoma de Mexico, Ciudad Universitaria, Ciudad de México, MéxicoUniversidad Nacional Autónoma de Mexico, Ciudad Universitaria, Ciudad de México, MéxicoInstituto de Ciencias del Mar (ICIMAR), La Habana, CubaDepartamento de Ciencias Farmacéuticas, Facultad de Ciencias, Universidad de Católica del Norte, Antofagasta, ChileInstituto de Ciencias del Mar (ICIMAR), La Habana, CubaPPES Lab, Proteinchemistry, Proteomics and Epigenetic Signaling, Department of Biomedical Sciences, University of Antwerp, Antwerp, BelgiumMarine plants are important sources of pharmacologically active metabolites. The aim of the present work was to evaluate the cytotoxic and antitumor activity of a polyphenolic fraction obtained from Thalassia testudinum marine plant and thalassiolin B in human colorectal cancer cells. Human cancer cell lines, including HCT15, HCT116, SW260, and HT29 were treated with tested products for cytotoxicity evaluation by crystal violet assay. The potential proapoptotic effect of these natural products was assessed by flow cytometry in HCT15 cells at 48 h using Annexin V-FITC/propidium iodide. In addition, reactive oxygen species (ROS) generation was measured by fluorescence using DCFH-DA staining, and sulfhydryl concentration by spectrophotometry. The in vivo antitumor activity of the polyphenolic fraction (25 mg/kg) was evaluated in a xenograft model in nu/nu mice. In vivo proapoptotic effect was also evaluated by immunohistochemistry using anti-caspase 3 and anti-Bcl-2 antibodies. The results showed that tested products exert colorectal cancer cell cytotoxicity. Besides, the tested products induced a significant increase (p < 0.05) of intracellular ROS generation, and a depletion of sulfhydryl concentration in HCT15 cells. The polyphenolic fraction arrested tumor growth and induced apoptosis in the xenograft mice model. These results demonstrate the cytotoxic activity of T. testudinum metabolites associated, at least, with ROS overproduction and pro-apoptotic effects. Here we demonstrated for the first time the antitumor activity of a T. testudinum polar extract in a xenograft mice model. These results suggest the potential use of T. testudinum marine plant metabolites as adjuvant treatment in cancer therapy.https://www.frontiersin.org/articles/10.3389/fphar.2020.592985/fullT. testudinumpolyphenolsthalassiolin Bcolorectal cancerreactive oxygen speciesapoptosis
spellingShingle Livan Delgado-Roche
Livan Delgado-Roche
Kethia González
Fernando Mesta
Beatriz Couder
Zaira Tavarez
Ruby Zavala
Ivones Hernandez
Gabino Garrido
Idania Rodeiro
Wim Vanden Berghe
Polyphenolic Fraction Obtained From Thalassia testudinum Marine Plant and Thalassiolin B Exert Cytotoxic Effects in Colorectal Cancer Cells and Arrest Tumor Progression in a Xenograft Mouse Model
Frontiers in Pharmacology
T. testudinum
polyphenols
thalassiolin B
colorectal cancer
reactive oxygen species
apoptosis
title Polyphenolic Fraction Obtained From Thalassia testudinum Marine Plant and Thalassiolin B Exert Cytotoxic Effects in Colorectal Cancer Cells and Arrest Tumor Progression in a Xenograft Mouse Model
title_full Polyphenolic Fraction Obtained From Thalassia testudinum Marine Plant and Thalassiolin B Exert Cytotoxic Effects in Colorectal Cancer Cells and Arrest Tumor Progression in a Xenograft Mouse Model
title_fullStr Polyphenolic Fraction Obtained From Thalassia testudinum Marine Plant and Thalassiolin B Exert Cytotoxic Effects in Colorectal Cancer Cells and Arrest Tumor Progression in a Xenograft Mouse Model
title_full_unstemmed Polyphenolic Fraction Obtained From Thalassia testudinum Marine Plant and Thalassiolin B Exert Cytotoxic Effects in Colorectal Cancer Cells and Arrest Tumor Progression in a Xenograft Mouse Model
title_short Polyphenolic Fraction Obtained From Thalassia testudinum Marine Plant and Thalassiolin B Exert Cytotoxic Effects in Colorectal Cancer Cells and Arrest Tumor Progression in a Xenograft Mouse Model
title_sort polyphenolic fraction obtained from thalassia testudinum marine plant and thalassiolin b exert cytotoxic effects in colorectal cancer cells and arrest tumor progression in a xenograft mouse model
topic T. testudinum
polyphenols
thalassiolin B
colorectal cancer
reactive oxygen species
apoptosis
url https://www.frontiersin.org/articles/10.3389/fphar.2020.592985/full
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