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...
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Frontiers Media S.A.
2021
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oai:doaj.org-article:2c2ad57042394ebf8e1555cab89113022021-12-03T06:16:31ZAntiproliferative, Antiangiogenic, and Antimetastatic Therapy Response by Mangiferin in a Syngeneic Immunocompetent Colorectal Cancer Mouse Model Involves Changes in Mitochondrial Energy Metabolism1663-981210.3389/fphar.2021.670167https://doaj.org/article/2c2ad57042394ebf8e1555cab89113022021-12-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fphar.2021.670167/fullhttps://doaj.org/toc/1663-9812In 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.Julio César Rodriguez-GonzalezIvones Hernández-BalmasedaKen DeclerckClaudina Pérez-NovoEmilie LogieClaudia TheysPatrycja JakubekPatrycja JakubekOlga Luisa Quiñones-MazaGeovanni Dantas-CassaliDiego Carlos dos ReisGuy Van CampMiriam Teresa Lopes PazIdania Rodeiro-GuerraRené Delgado-HernándezRené Delgado-HernándezWim Vanden BergheFrontiers Media S.A.articleMangiferin (PubChem CID: 5081647)antitumorantiangiogenesisantimetastasiccolon carcinomamitochondrial metabolismTherapeutics. PharmacologyRM1-950ENFrontiers in Pharmacology, Vol 12 (2021) |
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| collection |
DOAJ |
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| topic |
Mangiferin (PubChem CID: 5081647) antitumor antiangiogenesis antimetastasic colon carcinoma mitochondrial metabolism Therapeutics. Pharmacology RM1-950 |
| spellingShingle |
Mangiferin (PubChem CID: 5081647) antitumor antiangiogenesis antimetastasic colon carcinoma mitochondrial metabolism Therapeutics. Pharmacology RM1-950 Julio César Rodriguez-Gonzalez Ivones Hernández-Balmaseda Ken Declerck Claudina Pérez-Novo Emilie Logie Claudia Theys Patrycja Jakubek Patrycja Jakubek Olga Luisa Quiñones-Maza Geovanni Dantas-Cassali Diego Carlos dos Reis Guy Van Camp Miriam Teresa Lopes Paz Idania Rodeiro-Guerra René Delgado-Hernández René Delgado-Hernández Wim Vanden Berghe Antiproliferative, Antiangiogenic, and Antimetastatic Therapy Response by Mangiferin in a Syngeneic Immunocompetent Colorectal Cancer Mouse Model Involves Changes in Mitochondrial Energy Metabolism |
| 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 |
article |
| author |
Julio César Rodriguez-Gonzalez Ivones Hernández-Balmaseda Ken Declerck Claudina Pérez-Novo Emilie Logie Claudia Theys Patrycja Jakubek Patrycja Jakubek Olga Luisa Quiñones-Maza Geovanni Dantas-Cassali Diego Carlos dos Reis Guy Van Camp Miriam Teresa Lopes Paz Idania Rodeiro-Guerra René Delgado-Hernández René Delgado-Hernández Wim Vanden Berghe |
| author_facet |
Julio César Rodriguez-Gonzalez Ivones Hernández-Balmaseda Ken Declerck Claudina Pérez-Novo Emilie Logie Claudia Theys Patrycja Jakubek Patrycja Jakubek Olga Luisa Quiñones-Maza Geovanni Dantas-Cassali Diego Carlos dos Reis Guy Van Camp Miriam Teresa Lopes Paz Idania Rodeiro-Guerra René Delgado-Hernández René Delgado-Hernández Wim Vanden Berghe |
| author_sort |
Julio César Rodriguez-Gonzalez |
| title |
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_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_sort |
antiproliferative, antiangiogenic, and antimetastatic therapy response by mangiferin in a syngeneic immunocompetent colorectal cancer mouse model involves changes in mitochondrial energy metabolism |
| publisher |
Frontiers Media S.A. |
| publishDate |
2021 |
| url |
https://doaj.org/article/2c2ad57042394ebf8e1555cab8911302 |
| work_keys_str_mv |
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