Cargando…

Antiproliferative, Antiangiogenic, and Antimetastatic Therapy Response by Mangiferin in a Syngeneic Immunocompetent Colorectal Cancer Mouse Model Involves Changes in Mitochondrial Energy Metabolism

In spite of the current advances and achievements in cancer treatments, colorectal cancer (CRC) persists as one of the most prevalent and deadly tumor types in both men and women worldwide. Drug resistance, adverse side effects and high rate of angiogenesis, metastasis and tumor relapse remain one o...

Descripción completa

Detalles Bibliográficos
Autores principales: Rodriguez-Gonzalez, Julio César, Hernández-Balmaseda, Ivones, Declerck, Ken, Pérez-Novo, Claudina, Logie, Emilie, Theys, Claudia, Jakubek, Patrycja, Quiñones-Maza, Olga Luisa, Dantas-Cassali, Geovanni, Carlos dos Reis, Diego, Van Camp, Guy, Lopes Paz, Miriam Teresa, Rodeiro-Guerra, Idania, Delgado-Hernández, René, Vanden Berghe, Wim
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8678272/
https://www.ncbi.nlm.nih.gov/pubmed/34924998
http://dx.doi.org/10.3389/fphar.2021.670167
_version_ 1784616295839301632
author Rodriguez-Gonzalez, Julio César
Hernández-Balmaseda, Ivones
Declerck, Ken
Pérez-Novo, Claudina
Logie, Emilie
Theys, Claudia
Jakubek, Patrycja
Quiñones-Maza, Olga Luisa
Dantas-Cassali, Geovanni
Carlos dos Reis, Diego
Van Camp, Guy
Lopes Paz, Miriam Teresa
Rodeiro-Guerra, Idania
Delgado-Hernández, René
Vanden Berghe, Wim
author_facet Rodriguez-Gonzalez, Julio César
Hernández-Balmaseda, Ivones
Declerck, Ken
Pérez-Novo, Claudina
Logie, Emilie
Theys, Claudia
Jakubek, Patrycja
Quiñones-Maza, Olga Luisa
Dantas-Cassali, Geovanni
Carlos dos Reis, Diego
Van Camp, Guy
Lopes Paz, Miriam Teresa
Rodeiro-Guerra, Idania
Delgado-Hernández, René
Vanden Berghe, Wim
author_sort Rodriguez-Gonzalez, Julio César
collection PubMed
description In spite of the current advances and achievements in cancer treatments, colorectal cancer (CRC) persists as one of the most prevalent and deadly tumor types in both men and women worldwide. Drug resistance, adverse side effects and high rate of angiogenesis, metastasis and tumor relapse remain one of the greatest challenges in long-term management of CRC and urges need for new leads of anticancer drugs. We demonstrate that CRC treatment with the phytopharmaceutical mangiferin (MGF), a glucosylxanthone present in Mango tree stem bark and leaves (Mangifera Indica L.), induces dose-dependent tumor regression and decreases lung metastasis in a syngeneic immunocompetent allograft mouse model of murine CT26 colon carcinoma, which increases overall survival of mice. Antimetastatic and antiangiogenic MGF effects could be further validated in a wound healing in vitro model in human HT29 cells and in a matrigel plug implant mouse model. Interestingly, transcriptome pathway enrichment analysis demonstrates that MGF inhibits tumor growth, metastasis and angiogenesis by multi-targeting of mitochondrial oxidoreductase and fatty acid β-oxidation metabolism, PPAR, SIRT, NFκB, Stat3, HIF, Wnt and GP6 signaling pathways. MGF effects on fatty acid β-oxidation metabolism and carnitine palmitoyltransferase 1 (CPT1) protein expression could be further confirmed in vitro in human HT29 colon cells. In conclusion, antitumor, antiangiogenic and antimetastatic effects of MGF treatment hold promise to reduce adverse toxicity and to mitigate therapeutic outcome of colorectal cancer treatment by targeting mitochondrial energy metabolism in the tumor microenvironment.
format Online
Article
Text
id pubmed-8678272
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-86782722021-12-18 Antiproliferative, Antiangiogenic, and Antimetastatic Therapy Response by Mangiferin in a Syngeneic Immunocompetent Colorectal Cancer Mouse Model Involves Changes in Mitochondrial Energy Metabolism Rodriguez-Gonzalez, Julio César Hernández-Balmaseda, Ivones Declerck, Ken Pérez-Novo, Claudina Logie, Emilie Theys, Claudia Jakubek, Patrycja Quiñones-Maza, Olga Luisa Dantas-Cassali, Geovanni Carlos dos Reis, Diego Van Camp, Guy Lopes Paz, Miriam Teresa Rodeiro-Guerra, Idania Delgado-Hernández, René Vanden Berghe, Wim Front Pharmacol Pharmacology In spite of the current advances and achievements in cancer treatments, colorectal cancer (CRC) persists as one of the most prevalent and deadly tumor types in both men and women worldwide. Drug resistance, adverse side effects and high rate of angiogenesis, metastasis and tumor relapse remain one of the greatest challenges in long-term management of CRC and urges need for new leads of anticancer drugs. We demonstrate that CRC treatment with the phytopharmaceutical mangiferin (MGF), a glucosylxanthone present in Mango tree stem bark and leaves (Mangifera Indica L.), induces dose-dependent tumor regression and decreases lung metastasis in a syngeneic immunocompetent allograft mouse model of murine CT26 colon carcinoma, which increases overall survival of mice. Antimetastatic and antiangiogenic MGF effects could be further validated in a wound healing in vitro model in human HT29 cells and in a matrigel plug implant mouse model. Interestingly, transcriptome pathway enrichment analysis demonstrates that MGF inhibits tumor growth, metastasis and angiogenesis by multi-targeting of mitochondrial oxidoreductase and fatty acid β-oxidation metabolism, PPAR, SIRT, NFκB, Stat3, HIF, Wnt and GP6 signaling pathways. MGF effects on fatty acid β-oxidation metabolism and carnitine palmitoyltransferase 1 (CPT1) protein expression could be further confirmed in vitro in human HT29 colon cells. In conclusion, antitumor, antiangiogenic and antimetastatic effects of MGF treatment hold promise to reduce adverse toxicity and to mitigate therapeutic outcome of colorectal cancer treatment by targeting mitochondrial energy metabolism in the tumor microenvironment. Frontiers Media S.A. 2021-12-03 /pmc/articles/PMC8678272/ /pubmed/34924998 http://dx.doi.org/10.3389/fphar.2021.670167 Text en Copyright © 2021 Rodriguez-Gonzalez, Hernández-Balmaseda, Declerck, Pérez-Novo, Logie, Theys, Jakubek, Quiñones-Maza, Dantas-Cassali, Carlos dos Reis, Van Camp, Lopes Paz, Rodeiro-Guerra, Delgado-Hernández and Vanden Berghe. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Rodriguez-Gonzalez, Julio César
Hernández-Balmaseda, Ivones
Declerck, Ken
Pérez-Novo, Claudina
Logie, Emilie
Theys, Claudia
Jakubek, Patrycja
Quiñones-Maza, Olga Luisa
Dantas-Cassali, Geovanni
Carlos dos Reis, Diego
Van Camp, Guy
Lopes Paz, Miriam Teresa
Rodeiro-Guerra, Idania
Delgado-Hernández, René
Vanden Berghe, Wim
Antiproliferative, Antiangiogenic, and Antimetastatic Therapy Response by Mangiferin in a Syngeneic Immunocompetent Colorectal Cancer Mouse Model Involves Changes in Mitochondrial Energy Metabolism
title Antiproliferative, Antiangiogenic, and Antimetastatic Therapy Response by Mangiferin in a Syngeneic Immunocompetent Colorectal Cancer Mouse Model Involves Changes in Mitochondrial Energy Metabolism
title_full Antiproliferative, Antiangiogenic, and Antimetastatic Therapy Response by Mangiferin in a Syngeneic Immunocompetent Colorectal Cancer Mouse Model Involves Changes in Mitochondrial Energy Metabolism
title_fullStr Antiproliferative, Antiangiogenic, and Antimetastatic Therapy Response by Mangiferin in a Syngeneic Immunocompetent Colorectal Cancer Mouse Model Involves Changes in Mitochondrial Energy Metabolism
title_full_unstemmed Antiproliferative, Antiangiogenic, and Antimetastatic Therapy Response by Mangiferin in a Syngeneic Immunocompetent Colorectal Cancer Mouse Model Involves Changes in Mitochondrial Energy Metabolism
title_short Antiproliferative, Antiangiogenic, and Antimetastatic Therapy Response by Mangiferin in a Syngeneic Immunocompetent Colorectal Cancer Mouse Model Involves Changes in Mitochondrial Energy Metabolism
title_sort antiproliferative, antiangiogenic, and antimetastatic therapy response by mangiferin in a syngeneic immunocompetent colorectal cancer mouse model involves changes in mitochondrial energy metabolism
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8678272/
https://www.ncbi.nlm.nih.gov/pubmed/34924998
http://dx.doi.org/10.3389/fphar.2021.670167
work_keys_str_mv AT rodriguezgonzalezjuliocesar antiproliferativeantiangiogenicandantimetastatictherapyresponsebymangiferininasyngeneicimmunocompetentcolorectalcancermousemodelinvolveschangesinmitochondrialenergymetabolism
AT hernandezbalmasedaivones antiproliferativeantiangiogenicandantimetastatictherapyresponsebymangiferininasyngeneicimmunocompetentcolorectalcancermousemodelinvolveschangesinmitochondrialenergymetabolism
AT declerckken antiproliferativeantiangiogenicandantimetastatictherapyresponsebymangiferininasyngeneicimmunocompetentcolorectalcancermousemodelinvolveschangesinmitochondrialenergymetabolism
AT pereznovoclaudina antiproliferativeantiangiogenicandantimetastatictherapyresponsebymangiferininasyngeneicimmunocompetentcolorectalcancermousemodelinvolveschangesinmitochondrialenergymetabolism
AT logieemilie antiproliferativeantiangiogenicandantimetastatictherapyresponsebymangiferininasyngeneicimmunocompetentcolorectalcancermousemodelinvolveschangesinmitochondrialenergymetabolism
AT theysclaudia antiproliferativeantiangiogenicandantimetastatictherapyresponsebymangiferininasyngeneicimmunocompetentcolorectalcancermousemodelinvolveschangesinmitochondrialenergymetabolism
AT jakubekpatrycja antiproliferativeantiangiogenicandantimetastatictherapyresponsebymangiferininasyngeneicimmunocompetentcolorectalcancermousemodelinvolveschangesinmitochondrialenergymetabolism
AT quinonesmazaolgaluisa antiproliferativeantiangiogenicandantimetastatictherapyresponsebymangiferininasyngeneicimmunocompetentcolorectalcancermousemodelinvolveschangesinmitochondrialenergymetabolism
AT dantascassaligeovanni antiproliferativeantiangiogenicandantimetastatictherapyresponsebymangiferininasyngeneicimmunocompetentcolorectalcancermousemodelinvolveschangesinmitochondrialenergymetabolism
AT carlosdosreisdiego antiproliferativeantiangiogenicandantimetastatictherapyresponsebymangiferininasyngeneicimmunocompetentcolorectalcancermousemodelinvolveschangesinmitochondrialenergymetabolism
AT vancampguy antiproliferativeantiangiogenicandantimetastatictherapyresponsebymangiferininasyngeneicimmunocompetentcolorectalcancermousemodelinvolveschangesinmitochondrialenergymetabolism
AT lopespazmiriamteresa antiproliferativeantiangiogenicandantimetastatictherapyresponsebymangiferininasyngeneicimmunocompetentcolorectalcancermousemodelinvolveschangesinmitochondrialenergymetabolism
AT rodeiroguerraidania antiproliferativeantiangiogenicandantimetastatictherapyresponsebymangiferininasyngeneicimmunocompetentcolorectalcancermousemodelinvolveschangesinmitochondrialenergymetabolism
AT delgadohernandezrene antiproliferativeantiangiogenicandantimetastatictherapyresponsebymangiferininasyngeneicimmunocompetentcolorectalcancermousemodelinvolveschangesinmitochondrialenergymetabolism
AT vandenberghewim antiproliferativeantiangiogenicandantimetastatictherapyresponsebymangiferininasyngeneicimmunocompetentcolorectalcancermousemodelinvolveschangesinmitochondrialenergymetabolism