Mangiferin induced fatty acid b-oxidation and ketogenic metabolism promote antiproliferative, antiangiogenic and antimetastatic therapeutic effects in a preclinical colorectal cancer mouse model
Creators
- 1. Centro de Investigación y Desarrollo de Medicamentos (CIDEM), Ave 26 entre Boyeros y Puentes Grandes, Plaza de la Revolución, La Habana, Cuba
- 2. Laboratorio de Farmacología, Instituto de Ciencias del Mar (ICIMAR), CITMA, Loma 14, Alturas del Vedado, Plaza de la Revolución, La Habana, Cuba
- 3. Laboratory of Protein Science, Proteomics and Epigenetic Signaling (PPES) and Integrated Personalized and Precision Oncology Network (IPPON), Department of Biomedical Sciences, University of Antwerp, Campus Drie Eiken, S4.25, Universiteitsplein 1, 2610, Antwerp, Belgium
- 4. Department of Chemistry, Technology and Biochemistry of Food, Gdansk University of Technology
- 5. Centre of Medical Genetics, University of Antwerp and Antwerp University Hospital, Prins Boudewijnlaan 43, 2650 Antwerp, Belgium
- 6. Departamento de Farmacología, Instituto de Ciencias Biológicas (ICB), Universidad Federal de Minas Gerais (UFMG), Avda. Antonio Carlos 6627, Belo Horizonte, Minas Gerais, Brasil
- 7. Centro de Estudios para las Investigaciones y Evaluaciones Biológicas (CEIEB), Instituto de Farmacia y Alimentos (IFAL), Universidad de La Habana, (UH). Ave. 23 # 21425 entre 214 and 222, La Coronela, La Lisa, PO 13600, La Habana, Cuba
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 anti-cancer drugs. Plant-derived natural products have
historically been a major source of novel anti-cancer phytopharmaceuticals. We demonstrate
that CRC treatment with 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 subcutaneous allograft mouse model with CT26
colon cancer cells, which increases overall survival of mice. MGF treatment also elicits antiangiogenic
effects in the matrigel plug implant mouse model. Interestingly, transcriptome and
pathway enrichment analysis demonstrates that MGF induced fatty acid b-oxidation
generates ketogenic metabolism which inhibits tumor growth, metastasis and angiogenesis
by multi-targeting of PPAR, NFκB, Stat3, HIF, HDAC/SIRT, Wnt and GP6 signaling pathways.
In conclusion, MGF holds promise as a novel class of ketogenic diet mimetic
phytopharmaceutical compounds which promote therapeutic antitumor, antiangiogenic and
antimetastatic effects in a preclinical colorectal cancer mouse model.
Notes
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