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Antiproliferative, Antiangiogenic, and Antimetastatic Therapy Response by Mangiferin in a Syngeneic Immunocompetent Colorectal Cancer Mouse Model Involves Changes in Mitochondrial Energy Metabolism
Abstract
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 multitargeting 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.
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Authors (15)
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César Julio Rodriguez-Gonzalez mgr
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Ivones Hernández-Balmaseda
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Ken Declerck
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Claudina Pérez-Novo PhD
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Emilie Logie
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Claudia Theys
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Luisa Olga Quiñones-Maza
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Geovanni Dantas-Cassali
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Diego Carlos dos Reis
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Guy Van Camp
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Miriam Teresa Lopes Paz
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Idania Rodeiro-Guerra
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René Delgado-Hernández
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Wim Vanden Berghe prof.
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Full text
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- Accepted or Published Version
- DOI:
- Digital Object Identifier (open in new tab) 10.3389/fphar.2021.670167
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Details
- Category:
- Articles
- Type:
- artykuły w czasopismach
- Published in:
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Frontiers in Pharmacology
no. 12,
ISSN: 1663-9812 - Language:
- English
- Publication year:
- 2021
- Bibliographic description:
- Rodriguez-Gonzalez C. J., Hernández-Balmaseda I., Declerck K., Pérez-Novo C., Logie E., Theys C., Jakubek P., Quiñones-Maza L. O., Dantas-Cassali G., dos Reis D. C., Van Camp G., Lopes Paz M. T., Rodeiro-Guerra I., Delgado-Hernández R., Vanden Berghe W.: Antiproliferative, Antiangiogenic, and Antimetastatic Therapy Response by Mangiferin in a Syngeneic Immunocompetent Colorectal Cancer Mouse Model Involves Changes in Mitochondrial Energy Metabolism// Frontiers in Pharmacology -Vol. 12, (2021), s.670167-
- DOI:
- Digital Object Identifier (open in new tab) 10.3389/fphar.2021.670167
- Verified by:
- Gdańsk University of Technology
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