Restoring physiological levels of ascorbate slows tumor growth and moderates HIF-1 pathway activity in Gulo-/- mice

Cancer Medicine

Volumn 4, Issue 2, 2015, Pages 303-314

  Campbell, Elizabeth J ^a   Vissers, Margreet C M ^a   Bozonet, Stephanie ^a   Dyer, Arron ^a   Robinson, Bridget A ^a,b   Dachs, Gabi U ^a  

^a UNIVERSITY OF OTAGO   (New Zealand)

^b CANTERBURY DISTRICT HEALTH BOARD   (New Zealand)

Author keywords

Gulonolactone oxidase; Hypoxia inducible factor 1; VEGF; Vitamin C

Indexed keywords

ASCORBIC ACID; CARBONATE DEHYDRATASE IX; DRINKING WATER; GLUCOSE TRANSPORTER 1; HYPOXIA INDUCIBLE FACTOR 1ALPHA; VASCULOTROPIN; HIF1A PROTEIN, MOUSE; SLC2A1 PROTEIN, MOUSE; VITAMIN;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CANCER INHIBITION; CONTROLLED STUDY; DIET SUPPLEMENTATION; DOWN REGULATION; HISTOPATHOLOGY; LEWIS CARCINOMA; MELANOMA; MOLECULAR PATHOLOGY; MOUSE; NECROSIS; NONHUMAN; PRIORITY JOURNAL; TISSUE LEVEL; TUMOR GROWTH; ANIMAL; C57BL MOUSE; CELL PROLIFERATION; DISEASE MODEL; DOSE RESPONSE; DRUG EFFECTS; EXPERIMENTAL MELANOMA; GENE EXPRESSION REGULATION; METABOLISM; SIGNAL TRANSDUCTION; TRANSGENIC MOUSE;

ANIMALS; ASCORBIC ACID; CARCINOMA, LEWIS LUNG; CELL PROLIFERATION; DISEASE MODELS, ANIMAL; DOSE-RESPONSE RELATIONSHIP, DRUG; GENE EXPRESSION REGULATION, NEOPLASTIC; GLUCOSE TRANSPORTER TYPE 1; HYPOXIA-INDUCIBLE FACTOR 1, ALPHA SUBUNIT; MELANOMA, EXPERIMENTAL; MICE; MICE, INBRED C57BL; MICE, TRANSGENIC; SIGNAL TRANSDUCTION; VITAMINS;

EID: 84990310417     PISSN: None     EISSN: 20457634     Source Type: Journal    
DOI: 10.1002/cam4.349     Document Type: Article

References (49)

1. Brahimi-Horn, M. C., J. Chiche, and J. Pouyssegur . 2007. Hypoxia and cancer. J. Mol. Med. 85:1301-1307.
2. Ratcliffe, P. J. 2013. Oxygen sensing and hypoxia signalling pathways in animals: the implications of physiology for cancer. J. Physiol. 591(Pt. 8):2027-2042.
3. Semenza, G. L. 2013. HIF-1 mediates metabolic responses to intratumoral hypoxia and oncogenic mutations. J. Clin. Invest. 123:3664-3671.
4. Kim, J. W., and C. V. Dang . 2006. Cancer's molecular sweet tooth and the Warburg effect. Cancer Res. 66:8927-8930.
5. Maxwell, P. H., G. U. Dachs, J. M. Gleadle, L. G. Nicholls, A. L. Harris, I. J. Stratford, et al. 1997. Hypoxia-inducible factor-1 modulates gene expression in solid tumors and influences both angiogenesis and tumor growth. Proc. Natl. Acad. Sci. USA 94:8104-8109.
6. Semenza, G. L. 2012. Hypoxia-inducible factors: mediators of cancer progression and targets for cancer therapy. Trends Pharmacol. Sci. 33:207-214.
7. Zhong, H., A. M. De Marzo, E. Laughner, M. Lim, D. A. Hilton, D. Zagzag, et al. 1999. Overexpression of hypoxia-inducible factor 1alpha in common human cancers and their metastases. Cancer Res. 59:5830-5835.
8. Baba, Y., K. Nosho, K. Shima, N. Irahara, A. T. Chan, J. A. Meyerhardt, et al. 2010. HIF1A overexpression is associated with poor prognosis in a cohort of 731 colorectal cancers. Am. J. Pathol. 176:2292-2301.
9. Jaakkola, P., D. R. Mole, Y. M. Tian, M. I. Wilson, J. Gielbert, S. J. Gaskell, et al. 2001. Targeting of HIF-alpha to the von Hippel-Lindau ubiquitylation complex by O2-regulated prolyl hydroxylation. Science 292:468-472.
10. Yu, F., S. B. White, Q. Zhao, and F. S. Lee . 2001. Dynamic, site-specific interaction of hypoxia-inducible factor-1alpha with the von Hippel-Lindau tumor suppressor protein. Cancer Res. 61:4136-4142.
11. Lando, D., D. J. Peet, J. J. Gorman, D. A. Whelan, M. L. Whitelaw, and R. K. Bruick . 2002. FIH-1 is an asparaginyl hydroxylase enzyme that regulates the transcriptional activity of hypoxia-inducible factor. Genes Dev. 16:1466-1471.
12. Ozer, A., and R. K. Bruick . 2007. Non-heme dioxygenases: cellular sensors and regulators jelly rolled into one? Nat. Chem. Biol. 3:144-153.
13. Flashman, E., S. L. Davies, K. K. Yeoh, and C. J. Schofield . 2010. Investigating the dependence of the hypoxia-inducible factor hydroxylases (factor inhibiting HIF and prolyl hydroxylase domain 2) on ascorbate and other reducing agents. Biochem. J. 427:135-142.
14. Koivunen, P., M. Hirsila, V. Gunzler, K. I. Kivirikko, and J. Myllyharju . 2004. Catalytic properties of the asparaginyl hydroxylase (FIH) in the oxygen sensing pathway are distinct from those of its prolyl 4-hydroxylases. J. Biol. Chem. 279:9899-9904.
15. de Jong, L., S. P. Albracht, and A. Kemp . 1982. Prolyl 4-hydroxylase activity in relation to the oxidation state of enzyme-bound iron. The role of ascorbate in peptidyl proline hydroxylation. Biochim. Biophys. Acta 704:326-332.
16. Salnikow, K. 2007. The role of ascorbate in the modulation of HIF-1alpha protein and HIF-dependent transcription by chromium(VI) and nickel(II). Free Radic. Biol. Med. 42:1246-1257.
17. Knowles, H. J., R. R. Raval, A. L. Harris, and P. J. Ratcliffe . 2003. Effect of ascorbate on the activity of hypoxia-inducible factor in cancer cells. Cancer Res. 63:1764-1768.
18. Vissers, M. C., S. P. Gunningham, M. J. Morrison, G. U. Dachs, and M. J. Currie . 2007. Modulation of hypoxia-inducible factor-1 alpha in cultured primary cells by intracellular ascorbate. Free Radic. Biol. Med. 42:765-772.
19. Kuiper, C., G. U. Dachs, M. J. Currie, and M. C. Vissers . 2014. Intracellular ascorbate enhances hypoxia-inducible factor (HIF)-hydroxylase activity and preferentially suppresses the HIF-1 transcriptional response. Free Radic. Biol. Med. 69C:308-317.
20. Kuiper, C., I. G. Molenaar, G. U. Dachs, M. J. Currie, P. H. Sykes, and M. C. Vissers . 2010. Low ascorbate levels are associated with increased hypoxia-inducible factor-1 activity and an aggressive tumor phenotype in endometrial cancer. Cancer Res. 70:5749-5758.
21. Kuiper, C., G. U. Dachs, D. Munn, M. J. Currie, B. A. Robinson, J. F. Pearson, et al. 2014. Increased tumor ascorbate is associated with extended disease- free survival and decreased hypoxia-inducible factor-1 activation in human colorectal cancer. Front. Oncol. 4:10.
22. Gao, P., H. Zhang, R. Dinavahi, F. Li, Y. Xiang, V. Raman, et al. 2007. HIF-dependent antitumorigenic effect of antioxidants in vivo. Cancer Cell 12:230-238.
23. Chen, Q., M. G. Espey, A. Y. Sun, C. Pooput, K. L. Kirk, M. C. Krishna, et al. 2008. Pharmacologic doses of ascorbate act as a prooxidant and decrease growth of aggressive tumor xenografts in mice. Proc. Natl Acad. Sci. USA 105:11105-11109.
24. Pollard, H. B., M. A. Levine, O. Eidelman, and M. Pollard . 2010. Pharmacological ascorbic acid suppresses syngeneic tumor growth and metastases in hormone-refractory prostate cancer. In Vivo 24:249-255.
25. Levine, M., C. Conry-Cantilena, Y. Wang, R. W. Welch, P. W. Washko, K. R. Dhariwal, et al. 1996. Vitamin C pharmacokinetics in healthy volunteers: evidence for a recommended dietary allowance. Proc. Natl. Acad. Sci. USA 93:3704-3709.
26. Carr, A. C., S. M. Bozonet, J. M. Pullar, J. W. Simcock, and M. C. Vissers . 2013. Human skeletal muscle ascorbate is highly responsive to changes in vitamin C intake and plasma concentrations. Am. J. Clin. Nutr. 97:800-807.
27. Wilson, M. K., B. C. Baguley, C. Wall, M. B. Jameson, and M. P. Findlay . 2014. Review of high-dose intravenous vitamin C as an anticancer agent. Asia Pac. J. Clin. Oncol. 10:22-37.
28. Maeda, N., H. Hagihara, Y. Nakata, S. Hiller, J. Wilder, and R. Reddick . 2000. Aortic wall damage in mice unable to synthesize ascorbic acid. Proc. Natl. Acad. Sci. USA 97:841-846.
29. Vissers, M. C., S. M. Bozonet, J. F. Pearson, and L. J. Braithwaite . 2011. Dietary ascorbate intake affects steady state tissue concentrations in vitamin C-deficient mice: tissue deficiency after suboptimal intake and superior bioavailability from a food source (kiwifruit). Am. J. Clin. Nutr. 93:292-301.
30. Nytko, K. J., N. Maeda, P. Schläfli, P. Spielmann, R. H. Wenger, and D. P. Stiehl . 2011. Vitamin C is dispensable for oxygen sensing in vivo. Blood 117:5485-5493.
31. Telang, S., A. L. Clem, J. W. Eaton, and J. Chesney . 2007. Depletion of ascorbic acid restricts angiogenesis and retards tumor growth in a mouse model. Neoplasia 9:47-56.
32. Cha, J., M. W. Roomi, V. Ivanov, T. Kalinovsky, A. Niedzwiecki, and M. Rath . 2013. Ascorbate supplementation inhibits growth and metastasis of B16FO melanoma and 4T1 breast cancer cells in vitamin C-deficient mice. Int. J. Oncol. 42:55-64.
33. Workman, P., E. O. Aboagye, F. Balkwill, A. Balmain, G. Bruder, D. J. Chaplin, et al. 2010. Guidelines for the welfare and use of animals in cancer research. Br. J. Cancer 102:1555-1577.
34. Williams, K. J., B. A. Telfer, D. Xenaki, M. R. Sheridan, I. Desbaillets, H. J. Peters, et al. 2005. Enhanced response to radiotherapy in tumours deficient in the function of hypoxia induciblefactor-1. Radiother. Oncol. 75:89-98.
35. Schleicher, R. L., M. D. Carrol, E. S. Ford, and D. A. Lacher . 2009. Serum vitamin C and the prevalence of vitamin C deficiency in the United States: 2003-2004 National Health and Nutrition Examination Survey (NHANES). Am. J. Clin. Nutr. 90:1252-1263.
36. Rockenbach, G., P. F. Di Pietro, C. Ambrosi, B. C. Boaventura, F. G. Vieira, C. G. Crippa, et al. 2011. Dietary intake and oxidative stress in breast cancer: before and after treatments. Nutr. Hosp. 26:737-744.
37. Fain, O., E. Mathieu, and M. Thomas . 1998. Scurvy in patients with cancer. BMJ 316:1661-1662.
38. Bates, C. J., M. Hamer, and G. D. Mishra . 2011. Redox-modulatory vitamins and minerals that prospectively predict mortality in older British people: the National Diet and Nutrition Survey of people aged 65 years and over. Br. J. Nutr. 105:123-132.
39. Burns, J. J., E. H. Mosbach, and S. Schulenberg . 1954. Ascorbic acid synthesis in normal and drug-treated rats, studied with L-ascorbic-1-C14 acid. J. Biol. Chem. 207679-687.
40. Schorah, C. J., C. Downing, A. Piripitsi, L. Gallivan, A. H. Al-Hazaa, M. J. Sanderson, et al. 1996. Total vitamin C, ascorbic acid, and dehydroascorbic acid concentrations in plasma of critically ill patients. Am. J. Clin. Nutr. 63:760-765.
41. Handelman, G. J. 2007. Vitamin C deficiency in dialysis patients-are we perceiving the tip of an iceberg? Nephrol. Dial. Transplant. 22:328-331.
42. Berger, M. M. 2009. Vitamin C requirements in parenteral nutrition. Gastroenterology 137(5 Suppl.):S70-S78.
43. May, J. M. 2011. The SLC23 family of ascorbate transporters: ensuring that you get and keep your daily dose of vitamin C. Br. J. Pharmacol. 164:1793-1801.
44. Myllyharju, J. 2008. Prolyl 4-hydroxylases, key enzymes in the synthesis of collagens and regulation of the response to hypoxia, and their roles as treatment targets. Ann. Med. 40:402-417.
45. Minor, E. A., B. L. Court, J. I. Young, and G. Wang . 2013. Ascorbate induces ten-eleven translocation (Tet) methylcytosine dioxygenase-mediated generation of 5-hydroxymethylcytosine. J. Biol. Chem. 288:13669-13674.
46. Vissers, M. C., A. C. Carr, J. M. Pullar, and S. M. Bozonet . 2013. The bioavailability of vitamin C from kiwifruit. Adv. Food Nutr. Res. 68:125-147.
47. Carr, A. C., and B. Frei . 1999. Toward a new recommended dietary allowance for vitamin C based on antioxidant and health effects in humans. Am. J. Clin. Nutr. 69:1086-1107.
48. Mosdøl, A., B. Erens, and E. J. Brunner . 2008. Estimated prevalence and predictors of vitamin C deficiency within UK's low-income population. J. Public Health (Oxf) 30:456-460.
49. Mandl, J., A. Szarka, and G. Bánhegyi . 2009. Vitamin C: update on physiology and pharmacology. Br. J. Pharmacol. 157:1097-1110.