Display options
Cite
Nakagawa T, Lanaspa MA, Millan IS, et al. Fructose contributes to the Warburg effect for cancer growth. Cancer Metab. 2020;8:16doi: 10.1186/s40170-020-00222-9.
Nakagawa, T., Lanaspa, M. A., Millan, I. S., Fini, M., Rivard, C. J., Sanchez-Lozada, L. G., Andres-Hernando, A., Tolan, D. R., & Johnson, R. J. (2020). Fructose contributes to the Warburg effect for cancer growth. Cancer & metabolism, 816. https://doi.org/10.1186/s40170-020-00222-9
Nakagawa, Takahiko, et al. "Fructose contributes to the Warburg effect for cancer growth." Cancer & metabolism vol. 8 (2020): 16. doi: https://doi.org/10.1186/s40170-020-00222-9
Nakagawa T, Lanaspa MA, Millan IS, Fini M, Rivard CJ, Sanchez-Lozada LG, Andres-Hernando A, Tolan DR, Johnson RJ. Fructose contributes to the Warburg effect for cancer growth. Cancer Metab. 2020 Jul 10;8:16. doi: 10.1186/s40170-020-00222-9. eCollection 2020. PMID: 32670573; PMCID: PMC7350662.
Copy Download .nbib Format: NLM
Share it on

Cancer Metab. 2020 Jul 10;8:16. doi: 10.1186/s40170-020-00222-9. eCollection 2020.

Fructose contributes to the Warburg effect for cancer growth.

Cancer & metabolism

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

Affiliations

  1. Department of Nephrology, Rakuwakai Otowa Hospital, 2 Otowa-Chinji-cho, Yamashina-ku, Kyoto, Japan.
  2. Department of Stem Cell Biology & Regenerative Medicine, Shiga University of Medical Science, Otsu, Japan.
  3. Division of Renal Diseases and Hypertension, University of Colorado Denver, Aurora, CO USA.
  4. Department of Medicine, Division of Endocrinology, Metabolism and Diabetes, University of Colorado School of Medicine, Aurora, USA.
  5. University of Colorado Cancer Center, Aurora, CO USA.
  6. Department of Medical Oncology, University of Colorado Denver, Aurora, CO USA.
  7. Department of Cardio-Renal Physiopathology, Instituto Nacional de Cardiología Ignacio Chavez, 14080 Mexico City, CP Mexico.
  8. Department of Biology, Boston University, Boston, MA USA.

PMID: 32670573 PMCID: PMC7350662 DOI: 10.1186/s40170-020-00222-9

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.

© The Author(s) 2020.

Keywords: Cancer; Fructose; Hypoxia; Lactate; Mitochondria; Polyol pathway; Uric acid

Conflict of interest statement

Competing interestsMAL, DRT, LGL, CJR, and RJJ have equity in a start-up company developing fructokinase inhibitors (Colorado Research Partners LLC), and TN and RJJ also have equity with XORTX therape

References

  1. Biochem J. 1967 Sep;104(3):1040-7 - PubMed
  2. Ann Emerg Med. 1986 Dec;15(12):1470-7 - PubMed
  3. Biochim Biophys Acta. 1960 Jan 1;37:127-38 - PubMed
  4. Nature. 1998 Sep 17;395(6699):284-8 - PubMed
  5. Biochem J. 1970 Sep;119(3):501-10 - PubMed
  6. Eur J Cancer. 1999 Jul;35(7):1076-82 - PubMed
  7. J Am Soc Nephrol. 2020 May;31(5):898-906 - PubMed
  8. J Physiol. 1949 Aug;109(1-2):98-102 - PubMed
  9. Cell Metab. 2018 Feb 6;27(2):351-361.e3 - PubMed
  10. Nat Commun. 2013;4:2434 - PubMed
  11. J Gen Physiol. 1927 Mar 7;8(6):519-30 - PubMed
  12. Proc Natl Acad Sci U S A. 2012 Mar 13;109(11):4320-5 - PubMed
  13. Cancer Res. 1995 Mar 15;55(6):1373-8 - PubMed
  14. Stroke. 1992 Nov;23(11):1617-22 - PubMed
  15. Nat Clin Pract Nephrol. 2005 Dec;1(2):80-6 - PubMed
  16. J Physiol. 1949 Mar 15;108(2):117-26 - PubMed
  17. J Anim Sci. 1982 Jul;55(1):73-6 - PubMed
  18. BMB Rep. 2018 Sep;51(9):429-436 - PubMed
  19. Science. 1969 Jul 25;165(3891):402-3 - PubMed
  20. Nature. 2020 Mar;579(7800):586-591 - PubMed
  21. Diabetes. 1997 Feb;46(2):179-86 - PubMed
  22. FEBS Lett. 1976 Sep 15;68(1):8-14 - PubMed
  23. Cell Metab. 2020 Jul 7;32(1):117-127.e3 - PubMed
  24. Biochem Biophys Res Commun. 2018 Sep 10;503(3):1298-1306 - PubMed
  25. Brain Res. 2017 Feb 15;1657:312-322 - PubMed
  26. Nat Rev Cancer. 2004 Nov;4(11):891-9 - PubMed
  27. Kidney Int. 2014 Aug;86(2):294-302 - PubMed
  28. Am J Med Sci. 1989 May;297(5):294-9 - PubMed
  29. Cancer Epidemiol Biomarkers Prev. 2005 Jan;14(1):138-47 - PubMed
  30. J Clin Endocrinol Metab. 2005 Feb;90(2):1171-5 - PubMed
  31. PLoS One. 2012;7(10):e47948 - PubMed
  32. Science. 2017 Apr 21;356(6335):307-311 - PubMed
  33. JAMA. 2019 Jan 22;321(3):256-265 - PubMed
  34. Cell Metab. 2018 Jun 05;27(6):1249-1262.e4 - PubMed
  35. Cell Metab. 2019 Oct 1;30(4):735-753.e4 - PubMed
  36. Pancreas. 2009 Aug;38(6):706-12 - PubMed
  37. Brain Res. 1990 May 21;516(2):310-2 - PubMed
  38. Nat Commun. 2017 Feb 13;8:14181 - PubMed
  39. Cancer Res. 1991 Jun 15;51(12):3316-22 - PubMed
  40. Atherosclerosis. 2016 Oct;253:171-177 - PubMed
  41. J Biol Chem. 2012 Nov 23;287(48):40732-44 - PubMed
  42. J Cell Physiol. 2006 Jun;207(3):614-27 - PubMed
  43. Nat Genet. 2011 Jul 31;43(9):869-74 - PubMed
  44. Cancer Epidemiol Biomarkers Prev. 2005 Sep;14(9):2098-105 - PubMed
  45. Nephrol Dial Transplant. 2012 Feb;27(2):608-12 - PubMed
  46. Am J Clin Nutr. 2006 Nov;84(5):1171-6 - PubMed
  47. PLoS One. 2008 Aug 13;3(8):e2915 - PubMed
  48. Proc Natl Acad Sci U S A. 2010 May 11;107(19):8788-93 - PubMed
  49. Cancer Res. 2011 Apr 1;71(7):2550-60 - PubMed
  50. Nature. 2015 Jun 25;522(7557):444-449 - PubMed
  51. Gastroenterology. 2017 Sep;153(3):743-752 - PubMed
  52. Nat Cell Biol. 2016 May;18(5):561-71 - PubMed
  53. Biochem J. 1960 Feb;74:216-23 - PubMed
  54. Sports Med. 2017 Mar;47(Suppl 1):23-32 - PubMed
  55. J Am Soc Nephrol. 2014 Nov;25(11):2526-38 - PubMed
  56. Cancer Cell. 2016 Nov 14;30(5):779-791 - PubMed
  57. Biochem Biophys Res Commun. 2018 Jun 2;500(2):462-469 - PubMed
  58. Clin Biochem. 2010 Jan;43(1-2):198-207 - PubMed
  59. J Clin Invest. 2018 Feb 1;128(2):545-555 - PubMed
  60. Proc Natl Acad Sci U S A. 2018 Mar 20;115(12):3138-3143 - PubMed
  61. Biochem J. 2002 May 15;364(Pt 1):309-15 - PubMed
  62. Nat Rev Cancer. 2004 Jun;4(6):437-47 - PubMed
  63. Nutr Metab (Lond). 2012 Oct 02;9(1):89 - PubMed
  64. Am J Physiol Renal Physiol. 2006 Mar;290(3):F625-31 - PubMed
  65. J Clin Endocrinol Metab. 2019 Jul 1;104(7):3003-3011 - PubMed
  66. Am J Physiol Renal Physiol. 2016 Oct 1;311(4):F722-F730 - PubMed
  67. Int J Radiat Oncol Biol Phys. 2001 Oct 1;51(2):349-53 - PubMed
  68. Front Nutr. 2015 May 06;2:12 - PubMed
  69. Carcinogenesis. 2017 Feb 1;38(2):119-133 - PubMed
  70. J Natl Cancer Inst. 2003 Jun 18;95(12):914-6 - PubMed
  71. Obesity (Silver Spring). 2016 Feb;24(2):453-60 - PubMed
  72. Dev Cell. 2016 Mar 7;36(5):540-9 - PubMed
  73. Nat Rev Microbiol. 2005 Jan;3(1):36-46 - PubMed
  74. Proc Natl Acad Sci U S A. 1992 Aug 15;89(16):7556-60 - PubMed
  75. J Histochem Cytochem. 2009 Aug;57(8):763-74 - PubMed
  76. Cancer Res. 2016 Jan 1;76(1):24-9 - PubMed
  77. Med Sci Monit. 2006 Dec;12(12):CR525-529 - PubMed
  78. Science. 1956 Aug 10;124(3215):269-70 - PubMed
  79. Cancer Res. 2010 Aug 1;70(15):6368-76 - PubMed
  80. Am J Physiol. 1992 Sep;263(3 Pt 1):G312-8 - PubMed
  81. Science. 2019 Mar 22;363(6433):1345-1349 - PubMed
  82. Int J Oncol. 2010 Sep;37(3):615-22 - PubMed
  83. Biochem J. 1997 Jan 1;321 ( Pt 1):239-46 - PubMed
  84. J Clin Invest. 1969 Mar;48(3):574-83 - PubMed
  85. Cell. 2012 Apr 27;149(3):656-70 - PubMed
  86. Br J Cancer. 1955 Dec;9(4):539-49 - PubMed
  87. FASEB J. 1994 Apr 1;8(6):414-9 - PubMed
  88. Cell Death Dis. 2018 May 10;9(5):557 - PubMed
  89. Proc Natl Acad Sci U S A. 2012 Jun 19;109(25):E1619-28 - PubMed
  90. Bioconjug Chem. 2007 May-Jun;18(3):628-34 - PubMed
  91. Diabetes. 1998 Jun;47(6):867-73 - PubMed
  92. J Natl Cancer Inst. 2002 Sep 4;94(17):1293-300 - PubMed
  93. J Clin Invest. 1978 Oct;62(4):721-6 - PubMed
  94. Science. 1968 Sep 20;161(3847):1253-4 - PubMed
  95. J Cell Physiol. 2007 May;211(2):477-85 - PubMed
  96. J Intern Med. 2020 Mar;287(3):252-262 - PubMed
  97. Am J Kidney Dis. 2002 Sep;40(3):464-71 - PubMed
  98. Am J Physiol. 1987 Sep;253(3 Pt 1):G390-6 - PubMed
  99. Biochem J. 1993 Dec 15;296 ( Pt 3):785-96 - PubMed
  100. Proc Natl Acad Sci U S A. 1996 Mar 5;93(5):1847-52 - PubMed
  101. FASEB J. 2002 Feb;16(2):243-5 - PubMed
  102. Am J Clin Nutr. 2010 Nov;92(5):1071-9 - PubMed
  103. Nucl Med Biol. 2011 May;38(4):461-75 - PubMed
  104. Science. 1956 Feb 24;123(3191):309-14 - PubMed
  105. J Intern Med. 2017 Aug;282(2):202-204 - PubMed

Publication Types

Grant support