Fructose contributes to the Warburg effect for cancer growth
Abstract Obesity and metabolic syndrome are strongly associated with cancer, and these disorders may share a common mechanism. Recently, fructose has emerged as a driving force to develop obesity and metabolic syndrome. Thus, we assume that fructose may be the mechanism to explain why obesity and me...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2020-07-01
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| Series: | Cancer & Metabolism |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s40170-020-00222-9 |
| _version_ | 1818291726774697984 |
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| author | Takahiko Nakagawa Miguel A. Lanaspa Inigo San Millan Mehdi Fini Christopher J. Rivard Laura G. Sanchez-Lozada Ana Andres-Hernando Dean R. Tolan Richard J. Johnson |
| author_facet | Takahiko Nakagawa Miguel A. Lanaspa Inigo San Millan Mehdi Fini Christopher J. Rivard Laura G. Sanchez-Lozada Ana Andres-Hernando Dean R. Tolan Richard J. Johnson |
| author_sort | Takahiko Nakagawa |
| collection | DOAJ |
| description | Abstract Obesity and metabolic syndrome are strongly associated with cancer, and these disorders may share a common mechanism. Recently, fructose has emerged as a driving force to develop obesity and metabolic syndrome. Thus, we assume that fructose may be the mechanism to explain why obesity and metabolic syndrome are linked with cancer. Clinical and experimental evidence showed that fructose intake was associated with cancer growth and that fructose transporters are upregulated in various malignant tumors. Interestingly, fructose metabolism can be driven under low oxygen conditions, accelerates glucose utilization, and exhibits distinct effects as compared to glucose, including production of uric acid and lactate as major byproducts. Fructose promotes the Warburg effect to preferentially downregulate mitochondrial respiration and increases aerobic glycolysis that may aid metastases that initially have low oxygen supply. In the process, uric acid may facilitate carcinogenesis by inhibiting the TCA cycle, stimulating cell proliferation by mitochondrial ROS, and blocking fatty acid oxidation. Lactate may also contribute to cancer growth by suppressing fat oxidation and inducing oncogene expression. The ability of fructose metabolism to directly stimulate the glycolytic pathway may have been protective for animals living with limited access to oxygen, but may be deleterious toward stimulating cancer growth and metastasis for humans in modern society. Blocking fructose metabolism may be a novel approach for the prevention and treatment of cancer. |
| first_indexed | 2024-12-13T02:48:39Z |
| format | Article |
| id | doaj.art-28f0bb6a5bc74d3795be8b5f9ba50730 |
| institution | Directory Open Access Journal |
| issn | 2049-3002 |
| language | English |
| last_indexed | 2024-12-13T02:48:39Z |
| publishDate | 2020-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Cancer & Metabolism |
| spelling | doaj.art-28f0bb6a5bc74d3795be8b5f9ba507302022-12-22T00:02:06ZengBMCCancer & Metabolism2049-30022020-07-018111210.1186/s40170-020-00222-9Fructose contributes to the Warburg effect for cancer growthTakahiko Nakagawa0Miguel A. Lanaspa1Inigo San Millan2Mehdi Fini3Christopher J. Rivard4Laura G. Sanchez-Lozada5Ana Andres-Hernando6Dean R. Tolan7Richard J. Johnson8Department of Nephrology, Rakuwakai Otowa HospitalDivision of Renal Diseases and Hypertension, University of Colorado DenverDepartment of Medicine, Division of Endocrinology, Metabolism and Diabetes, University of Colorado School of MedicineUniversity of Colorado Cancer CenterDepartment of Medical Oncology, University of Colorado DenverDepartment of Cardio-Renal Physiopathology, Instituto Nacional de Cardiología Ignacio ChavezDivision of Renal Diseases and Hypertension, University of Colorado DenverDepartment of Biology, Boston UniversityDivision of Renal Diseases and Hypertension, University of Colorado DenverAbstract Obesity and metabolic syndrome are strongly associated with cancer, and these disorders may share a common mechanism. Recently, fructose has emerged as a driving force to develop obesity and metabolic syndrome. Thus, we assume that fructose may be the mechanism to explain why obesity and metabolic syndrome are linked with cancer. Clinical and experimental evidence showed that fructose intake was associated with cancer growth and that fructose transporters are upregulated in various malignant tumors. Interestingly, fructose metabolism can be driven under low oxygen conditions, accelerates glucose utilization, and exhibits distinct effects as compared to glucose, including production of uric acid and lactate as major byproducts. Fructose promotes the Warburg effect to preferentially downregulate mitochondrial respiration and increases aerobic glycolysis that may aid metastases that initially have low oxygen supply. In the process, uric acid may facilitate carcinogenesis by inhibiting the TCA cycle, stimulating cell proliferation by mitochondrial ROS, and blocking fatty acid oxidation. Lactate may also contribute to cancer growth by suppressing fat oxidation and inducing oncogene expression. The ability of fructose metabolism to directly stimulate the glycolytic pathway may have been protective for animals living with limited access to oxygen, but may be deleterious toward stimulating cancer growth and metastasis for humans in modern society. Blocking fructose metabolism may be a novel approach for the prevention and treatment of cancer.http://link.springer.com/article/10.1186/s40170-020-00222-9FructoseUric acidCancerHypoxiaMitochondriaLactate |
| spellingShingle | Takahiko Nakagawa Miguel A. Lanaspa Inigo San Millan Mehdi Fini Christopher J. Rivard Laura G. Sanchez-Lozada Ana Andres-Hernando Dean R. Tolan Richard J. Johnson Fructose contributes to the Warburg effect for cancer growth Cancer & Metabolism Fructose Uric acid Cancer Hypoxia Mitochondria Lactate |
| title | Fructose contributes to the Warburg effect for cancer growth |
| title_full | Fructose contributes to the Warburg effect for cancer growth |
| title_fullStr | Fructose contributes to the Warburg effect for cancer growth |
| title_full_unstemmed | Fructose contributes to the Warburg effect for cancer growth |
| title_short | Fructose contributes to the Warburg effect for cancer growth |
| title_sort | fructose contributes to the warburg effect for cancer growth |
| topic | Fructose Uric acid Cancer Hypoxia Mitochondria Lactate |
| url | http://link.springer.com/article/10.1186/s40170-020-00222-9 |
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