Ascorbic acid: Chemistry, biology and the treatment of cancer

Biochimica et Biophysica Acta - Reviews on Cancer

Volumn 1826, Issue 2, 2012, Pages 443-457

  Du, Juan ^a   Cullen, Joseph J ^a,b,c   Buettner, Garry R ^a,b  

^a UNIVERSITY OF IOWA   (United States)

^b UNIVERSITY OF IOWA HOSPITALS AND CLINICS   (United States)

^c VETERANS AFFAIRS MEDICAL CENTER   (United States)

Author keywords

Ascorbate; Cancer; Hydrogen peroxide; Nutrition; Oxidative stress; Pharmacology

Indexed keywords

ASCORBIC ACID; ERLOTINIB; GEMCITABINE; HYDROGEN PEROXIDE; HYPOXIA INDUCIBLE FACTOR; OXYGENASE;

ANTIOXIDANT ACTIVITY; ASCORBIC ACID METABOLISM; CANCER PREVENTION; CONTINUOUS INFUSION; CYTOTOXICITY; DEMETHYLATION; DOSE RESPONSE; DRUG BLOOD LEVEL; DRUG MECHANISM; DRUG MEGADOSE; DRUG POTENTIATION; DRUG STRUCTURE; DRUG UPTAKE; HUMAN; LEUKEMIA; LIVER CELL CARCINOMA; LUNG NON SMALL CELL CANCER; MALIGNANT NEOPLASTIC DISEASE; MAXIMUM PLASMA CONCENTRATION; NONHUMAN; PANCREAS CANCER; PRIORITY JOURNAL; REVIEW; SINGLE DRUG DOSE;

ANIMALS; ANTIOXIDANTS; ASCORBIC ACID; HISTONES; HUMANS; HYDROGEN PEROXIDE; NEOPLASMS;

EID: 84866613772     PISSN: 0304419X     EISSN: 18792561     Source Type: Journal    
DOI: 10.1016/j.bbcan.2012.06.003     Document Type: Review

References (267)

1. Svirbely J.L., Szent-Györgyi A. The chemical nature of vitamin C. Biochem. J. 1933, 27:279-285.
2. Buettner G.R., Schafer F.Q. Albert Szent-Györgyi: vitamin C identification. Biochemist 2006, 28:31-33.
3. Calcutt G. The formation of hydrogen peroxide during the autoxidation of ascorbic acid. Experientia 1951, 7:26.
4. Bielski B.H.J. Chemistry of ascorbic acid radicals. Ascorbic Acid: Chemistry, Metabolism, and Uses 1982, Vol. 200:81-100. American Chemical Society, Washington D.C. P.A. Seib, B.M. Tolbert (Eds.).
5. Khan M.M., Martell A.E. Metal ion and metal chelate catalyzed oxidation of ascorbic acid by molecular oxygen. II. Cupric and ferric chelate catalyzed oxidation. J. Am. Chem. Soc. 1967, 89:7104-7111.
6. Udenfriend S., Clark C.T., Axelrod J., Brodie B.B. Ascorbic acid in aromatic hydroxylation. I. A model system for aromatic hydroxylation. J. Biol. Chem. 1954, 208:731-739.
7. Graumlich J.F., Ludden T.M., Conry-Cantilena C., Cantilena L.R.J., Wang Y., Levine M. Pharmacokinetic model of ascorbic acid in healthy male volunteers during depletion and repletion. Pharm. Res. 1997, 14:1133-1139.
8. Padayatty S.J., Sun H., Wang Y., Riordan H.D., Hewitt S.M., Katz A., Wesley R.A., Levine M. Vitamin C pharmacokinetics: implications for oral and intravenous use. Ann. Intern. Med. 2004, 140:533-537.
9. Chen Q., Espey M.G., Krishna M.C., Mitchell J.B., Corpe C.P., Buettner G.R., Shacter E., Levine M. Pharmacologic ascorbic acid concentrations selectively kill cancer cells: action as a pro-drug to deliver hydrogen peroxide to tissues. Proc. Natl. Acad. Sci. U. S. A. 2005, 102:13604-13609.
10. Chen Q., Espey M.G., Sun A., Lee J., Krishna M.C., Shacter E., Choyke P.L., Pooput C., Kirk K.L., Buettner G.R., Levine M. Ascorbate in pharmacologic concentrations selectively generates ascorbate radical and hydrogen peroxide in extracellular fluid in vivo. Proc. Natl. Acad. Sci. U. S. A. 2007, 104:8749-8754.
11. Chen Q., Espey M.G., Sun A.Y., Pooput C., Kirk K.L., Krishna M.C., Khosh D.B., Drisko J., Levine M. Pharmacologic doses of ascorbate act as a prooxidant and decrease growth of aggressive tumor xenografts in mice. Proc. Natl. Acad. Sci. U. S. A. 2008, 105:11105-11109.
12. Du J., Martin S.M., Levine M., Wagner B.A., Buettner G.R., Wang S.H., Taghiyev A.F., Du C., Knudson C.M., Cullen J.J. Mechanisms of ascorbate-induced cytotoxicity in pancreatic cancer. Clin. Cancer Res. 2010, 16:509-520.
13. Buettner G.R. The pecking order of free radicals and antioxidants: lipid peroxidation, [alpha]-tocopherol, and ascorbate. Arch. Biochem. Biophys. 1993, 300:535-543.
14. Buettner G.R., Jurkiewicz B.A. Catalytic metals, ascorbate and free radicals: combinations to avoid. Radiat. Res. 1996, 145:532-541.
15. Buettner G.R. In the absence of catalytic metals ascorbate does not autoxidize at pH 7: ascorbate as a test for catalytic metals. J. Biochem. Biophys. Methods 1988, 16:27-40.
16. Song Y., Buettner G.R. Thermodynamic and kinetic considerations for the reaction of semiquinone radicals to form superoxide and hydrogen peroxide. Free Radic. Biol. Med. 2010, 49:919-962.
17. Williams N.H., Yandell J.K. Outer-sphere electron-transfer reactions of ascorbate anions. Aust. J. Chem. 1982, 35:1133-1144.
18. Buettner G.R. Ascorbate oxidation: UV absorbance of ascorbate and ESR spectroscopy of the ascorbyl radical as assays for iron. Free Radic. Res. Commun. 1990, 10:5-9.
19. Nishikimi M., Fukuyama R., Minoshima S., Shimizu N., Yagi K. Cloning and chromosomal mapping of the human nonfunctional gene for l-gulono-gamma-lactone oxidase, the enzyme for l-ascorbic acid biosynthesis missing in man. J. Biol. Chem. 1994, 269:13685-13688.
20. Vera J.C., Rivas C.I., Velasquez F.V., Zhang R.H., Concha I.I., Golde D.W. Resolution of the facilitated transport of dehydroascorbic acid from its intracellular accumulation as ascorbic acid. J. Biol. Chem. 1995, 270:23706-23712.
21. Savini I., Rossi A., Pierro C., Avigliano L., Catani M.V. SVCT1 and SVCT2: key proteins for vitamin C uptake. Amino Acids 2008, 34:347-355.
22. Welch R.W., Wang Y., Crossman A.J., Park J.B., Kirk K.L., Levine M. Accumulation of vitamin C (ascorbate) and its oxidized metabolite dehydroascorbic acid occurs by separate mechanisms. J. Biol. Chem. 1995, 270:12584-12592.
23. +-dependent co-transport. J. Biol. Chem. 1983, 258:12886-12894.
24. Welch R.W., Bergsten P., Butler J.D., Levine M. Ascorbic acid accumulation and transport in human fibroblasts. Biochem. J. 1993, 294:505-510.
25. +-dependent l-ascorbic acid transporters. Nature 1999, 399:70-75.
26. Corpe C.P., Tu H., Eck P., Wang J., Faulhaber-Walter R., Schnermann J., Margolis S., Padayatty S., Sun H., Wang Y., Nussbaum R.L., Espey M.G., Levine M. Vitamin C transporter Slc23a1 links renal reabsorption, vitamin C tissue accumulation, and perinatal survival in mice. J. Clin. Invest. 2010, 120:1069-1083.
27. Wilson J.X. Regulation of vitamin C transport. Annu. Rev. Nutr. 2005, 25:105-125.
28. Savini I., Catani M.V., Arnone R., Rossi A., Frega G., Del Principe D., Avigliano L. Translational control of the ascorbic acid transporter SVCT2 in human platelets. Free Radic. Biol. Med. 2007, 42:608-616.
29. MacDonald L., Thumser A.E., Sharp P. Decreased expression of the vitamin C transporter SVCT1 by ascorbic acid in a human intestinal epithelial cell line. Br. J. Nutr. 2002, 87:97-100.
30. +-dependent vitamin C transporter but not glucose transporter pathways. J. Biol. Chem. 2005, 280:5211-5220.
31. Schafer M., Werner S. Cancer as an overhealing wound: an old hypothesis revisited. Nat. Rev. Mol. Cell Biol. 2008, 9:628-638.
32. Agus D.B., Vera J.C., Golde D.W. Stromal cell oxidation: a mechanism by which tumors obtain vitamin C. Cancer Res. 1999, 59:4555-4558.
33. Malo C., Wilson J.X. Glucose modulates vitamin C transport in adult human small intestinal brush border membrane vesicles. J. Nutr. 2000, 130:63-69.
34. Rumsey S.C., Daruwala R., Al-Hasani H., Zarnowski M.J., Simpson I.A., Levine M. Dehydroascorbic acid transport by GLUT4 in Xenopus oocytes and isolated rat adipocytes. J. Biol. Chem. 2000, 275:28246-28253.
35. Cunningham J.J. The glucose/insulin system and vitamin C: implications in insulin-dependent diabetes mellitus. J. Am. Coll. Nutr. 1998, 17:105-108.
36. Sherry S., Ralli E.P. Further studies of the effects of insulin on the metabolism of vitamin C. J. Clin. Invest. 1948, 27:217-225.
37. Paolisso G., D'Amore A., Balbi V., Volpe C., Galzerano D., Giugliano D., Sgambato S., Varricchio M., D'Onofrio F. Plasma vitamin C affects glucose homeostasis in healthy subjects and in non-insulin-dependent diabetics. Am. J. Physiol. Endocrinol. Metab. 1994, 266:E261-E268.
38. May J.M., Qu Z.-C., Qiao H., Kouryab M.J. Maturational loss of the vitamin C transporter in erythrocytes. Biochem. Biophys. Res. Commun. 2007, 360:295-298.
39. Evans R.M., Currie L., Campbell A. The distribution of ascorbic acid between various cellular components of blood, in normal individuals, and its relation to the plasma concentration. Br. J. Nutr. 1982, 47:473-482.
40. Li H., Tu H., Wang Y., Levine M. Vitamin C in mouse and human red blood cells: an HPLC assay. Anal. Biochem. 2012, 426:109-117.
41. Levine M., Wang Y., Padayatty S.J., Morrow J. A new recommended dietary allowance of vitamin C for healthy young women. Proc. Natl. Acad. Sci. U. S. A. 2001, 98:9842-9846.
42. Lane D.J.R., Lawen A. Ascorbate and plasma membrane electron transport - enzymes vs efflux. Free Radic. Biol. Med. 2009, 47:485-495.
43. Wilson J.X. Antioxidant defense of the brain: a role for astrocytes. Can. J. Physiol. Pharmacol. 1997, 75:1149-1163.
44. Han O., Failla M.L., Hill A.D., Morris E.R., Smith J.C.J. Reduction of Fe(III) is required for uptake of nonheme iron by Caco-2 cells. J. Nutr. 1995, 125:1291-1299.
45. Hornig D. Distribution of ascorbic acid, metabolites and analogues in man and animals. Ann. N. Y. Acad. Sci. 1975, 258:103-118.
46. Kern H.L., Zolot S.L. Transport of vitamin C in the lens. Curr. Eye Res. 1987, 6:885-896.
47. Rumsey S.C., Levine M. Absorption, transport, and disposition of ascorbic acid in humans. J. Nutr. Biochem. 1998, 9:116-130.
48. Streeter M.L., Rosso P. Transport mechanisms for ascorbic acid in the human placenta. Am. J. Clin. Nutr. 1981, 34:1706-1711.
49. Brubaker R.F., Bourne W.M., Bachman L.A., McLaren J.W. Ascorbic acid content of human corneal epithelium. Invest. Ophthalmol. Vis. Sci. 2000, 41:1681-1683.
50. Van der Vliet A., O'Neill C.A., Cross C.E., Koostra J.M., Valz W.G., Halliwell B., Louie S. Determination of low-molecular-mass antioxidant concentrations in human respiratory tract lining fluids. Am. J. Physiol. Lung Cell Mol. Physiol. 1999, 276:L289-L296.
51. Bui M.H., Sauty A., Collet F., Leuenberger P. Dietary vitamin C intake and concentrations in the body fluids and cells of male smokers and nonsmokers. J. Nutr. 1992, 122:312-316.
52. May J.M., Qu Z., Li X. Ascorbic acid blunts oxidant stress due to menadione in endothelial cells. Arch. Biochem. Biophys. 2003, 411:136-144.
53. Chepda T., Cadau M., Girin P.H., Frey J., Chamson A. Monitoring of ascorbate at a constant rate in cell culture: effect on cell growth. In Vitro Cell. Dev. Biol. Anim. 2001, 37:26-30.
54. Vislisel J.M., Schafer F.Q., Buettner G.R. A simple and sensitive assay for ascorbate using a plate reader. Anal. Biochem. 2007, 365:31-39.
55. Washko P.W., Wang Y., Levine M. Ascorbic acid recycling in human neutrophils. J. Biol. Chem. 1993, 268:15531-15535.
56. Lloyd J.V., Davis P.S., Emery H., Lander H. Platelet ascorbic acid levels in normal subjects and disease. J. Clin. Pathol. 1972, 25:478-483.
57. Simpson G.L.W., Ortwerth B.J. The non-oxidative degradiation of ascorbic acid at physiological conditions. Biochim. Biophys. Acta 2000, 1501:12-24.
58. Bánhegyi G., Braun L., Csala M., Puskás F., Mandl J. Ascorbate metabolism and its regulation in animals. Free Radic. Biol. Med. 1997, 23:793-803.
59. Nagaraj R.H., Shamsi F.A., Huber B., Pischetsrieder M. Immunochemical detection of oxalate monokylamide, an ascorbate-derived Maillard reaction product in the human lens. FEBS J. 1999, 453:327-330.
60. Chai W., Liebman M., Kynast-Gales S., Massey L. Oxalate absorption and endogenous oxalate synthesis from ascorbate in calcium oxalate stone formers and non-stone formers. Am. J. Kidney Dis. 2004, 44:1060-1069.
61. Traxer O., Huet B., Poindexter J., Pak C.Y.C., Pearle M.S. Effect of ascorbic acid consumption on urinary stone risk factors. J. Urol. 2003, 170:397-401.
62. Robitaille L., Mamer O.A., Miller W.H.J., Levine M., Assouline S., Melnychuk D., Rousseau C., Hoffer L.J. Oxalic acid excretion after intravenous ascorbic acid administration. Metabolism 2009, 58:263-269.
63. Asplin J.R. Hyperoxaluric calcium nephrolithiasis. Endocrinol. Metab. Clin. North Am. 2002, 31:927-949.
64. Englard S., Seifter S. The biochemical functions of ascorbic acid. Annu. Rev. Nutr. 1986, 6:365-406.
65. Ozer A., Bruick R.K. Non-heme dioxygenases: cellular sensors and regulators jelly rolled into one?. Nat. Chem. Biol. 2007, 3:144-153.
66. Kivirikko K.I., Prockop D.J. Enzymatic hydroxylation of proline and lysine in protocollagen. Proc. Natl. Acad. Sci. U. S. A. 1967, 57:782-789.
67. Myllyharju J., Kivirikko K.I. Collagens, modifying enzymes and their mutations in humans, flies and worms. Trends Genet. 2004, 20:33-43.
68. Egeblad M., Rasch M.G., Weaver V.M. Dynamic interplay between the collagen scaffold and tumor evolution. Curr. Opin. Cell Biol. 2010, 22:697-706.
69. Liotta L.A. Tumor invasion and metastases-role of the extracellular matrix: Rhoads Memorial Award lecture. Cancer Res. 1986, 46:1-7.
70. Geesin J.C., Darr D., Kaufman R., Murad S., Pinnell S.R. Ascorbic acid specifically increases type I and type III procollagen messenger RNA levels in human skin fibroblasts. J. Investig. Dermatol. 1988, 90:420-424.
71. Cameron E., Pauling L., Leibovitz B. Ascorbic acid and cancer: a review. Cancer Res. 1979, 39:663-681.
72. Maeshima Y., Colorado P.C., Torre A., Holthaus K.A., Grunkemeyer J.A., Ericksen M.B., Hopfer H., Xiao Y., Stillman I.E., Kalluri R. Distinct antitumor properties of a type IV collagen domain derived from basement membrane. J. Biol. Chem. 2000, 275:21340-21348.
73. Bruick R.K., McKnight S.L. A conserved family of prolyl-4-hydroxylases that modify HIF. Science 2001, 294:1337-1340.
74. Kallio P.J., Wilson W.J., O'Brien S., Makino Y., Poellinger L. Regulation of the hypoxia-inducible transcription factor 1alpha by the ubiquitin-proteasome pathway. J. Biol. Chem. 1999, 274:6519-6525.
75. Hirsila M., Koivunen P., Gunzler V., Kivirikko K.I., Myllyharju J. Characterization of the human prolyl 4-hydroxylases that modify the hypoxia-inducible factor. J. Biol. Chem. 2003, 278:30772-30780.
76. Semenza G.L. Targeting HIF-1 for cancer therapy. Nat. Rev. Cancer 2003, 3:721-732.
77. Mole D.R., Blancher C., Copley R.R., Pollard P.J., Gleadle J.M., Ragoussis J., Ratcliffe P.J. Genome-wide association of hypoxia-inducible factor (HIF)-1α and HIF-2α DNA binding with expression profiling of hypoxia-inducible transcripts. J. Biol. Chem. 2009, 284:16767-16775.
78. Semenza G.L. Hypoxia-inducible factors: mediators of cancer progression and targets for cancer therapy. Trends Pharmacol. Sci. 2012, 33:207-214.
79. Gao P., Zhang H., Dinavahi R., Li F., Xiang Y., Raman V., Bhujwalla Z.M., Felsher D.W., Cheng L., Pevsner J., Lee L.A., Semenza G.L., Dang C.V. HIF-dependent antitumorigenic effect of antioxidants in vivo. Cancer Cell 2007, 12:230-238.
80. Lu H., Dalgard C.L., Mohyeldin A., McFate T., Tait A.S., Verma A. Reversible inactivation of HIF-1 prolyl hydroxylases allows cell metabolism to control basal HIF-1. J. Biol. Chem. 2005, 280:41928-41939.
81. Kuiper C., Molenaar I.G., Dachs G.U., Currie M.J., Sykes P.H., Vissers M.C. Low ascorbate levels are associated with increased hypoxia-inducible factor-1 activity and an aggressive tumor phenotype in endometrial cancer. Cancer Res. 2010, 70:5749-5758.
82. Mikirova N., Ichim T., Riordan N. Anti-angiogenic effect of high doses of ascorbic acid. J .Transl. Med. 2008, 6:50.
83. Pathi S.S., Lei P., Sreevalsan S., Chadalapaka G., Jutooru I., Safe S. Pharmacologic doses of ascorbic acid repress specificity protein (Sp) transcription factors and Sp-regulated genes in colon cancer cells. Nutr. Cancer 2011, 63:1133-1142.
84. Pagé E.L., Chan D.A., Giaccia A.J., Levine M., Richard D.E. Hypoxia-inducible factor-1α stabilization in nonhypoxic conditions: role of oxidation and intracellular ascorbate depletion. Mol. Biol. Cell 2008, 19:86-94.
85. Cloos P.A., Christensen J., Agger K., Helin K. Erasing the methyl mark: histone demethylases at the center of cellular differentiation and disease. Genes Dev. 2008, 22:1115-1140.
86. Chung T.-L., Brena R.M., Kolle G., Grimmond S.M., Berman B.P., Laird P.W., Pera M.F., Wolvetang E.J. Vitamin C promotes widespread yet specific DNA demethylation of the epigenome in human embryonic stem cells. Stem Cells 2010, 28:1848-1855.
87. Cyr A.R., Domann F.E. The redox basis of epigenetic modifications: from mechanisms to functional consequences. Antioxid. Redox Signal. 2011, 15:551-589.
88. Esteban M.A., Pei D. Vitamin C improves the quality of somatic cell reprogramming. Nat. Genet. 2012, 44:366-367.
89. Widschwendter M., Fiegl H., Egle D., Mueller-Holzner E., Spizzo G., Marth C., Weisenberger D.J., Campan M., Young J., Jacobs I., Laird P.W. Epigenetic stem cell signature in cancer. Nat. Genet. 2007, 39:157-158.
90. Verma M. Cancer control and prevention by nutrition and epigenetic approaches. Antioxid. Redox Signal. 2012, 17:355-364.
91. Block G. Vitamin C and cancer prevention: the epidemiologic evidence. Am. J. Clin. Nutr. 1991, 53:270S-282S.
92. Loria C.M., Klag M.J., Caulfield L.E., Whelton P.K. Vitamin C status and mortality in US adults. Am. J. Clin. Nutr. 2000, 72:139-145.
93. Patterson R.E., White E., Kristal A.R., Neuhouser M.L., Potter J.D. Vitamin supplements and cancer risk: the epidemiologic evidence. Cancer Causes Control 1997, 8:786-802.
94. Gey K.F. Vitamins E plus C and interacting conutrients required for optimal health. A critical and constructive review of epidemiology and supplementation data regarding cardiovascular disease and cancer. Biofactors 1998, 7:113-174.
95. Gonzalez C.A., Riboli E. Diet and cancer prevention: contributions from the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Euro. J. Cancer 2010, 46:2555-2562.
96. Musil F., Zadák Z., Solichová D., Hyšpler R., Kaška M., Sobotka L., Manák J. Dynamics of antioxidants in patients with acute pancreatitis and in patients operated for colorectal cancer: a clinical study. Nutrition 2005, 21:118-124.
97. Bjelakovic G., Nikolova D., Simonetti R.G., Gluud C. Antioxidant supplements for prevention of gastrointestinal cancers: a systematic review and meta-analysis. Lancet 2004, 364:1219-1228.
98. Gaziano J.M., Glynn R.J., Christen W.G., Kurth T., Belanger C., MacFadyen J., Bubes V., Manson J.E., Sesso H.D., Buring J.E. Vitamins E and C in the prevention of prostate and total cancer in men: the Physicians' Health Study II randomized controlled trial. JAMA 2009, 301:52-62.
99. Lin J., Cook N.R., Albert C., Zaharris E., Gaziano J.M., Van Denburgh M., Buring J.E., Manson J.E. Vitamins C and E and beta carotene supplementation and cancer risk: a randomized controlled trial. J. Natl. Cancer Inst. 2009, 101:14-23.
100. Heaney R.P. Nutrition, chronic disease, and the problem of proof. Am. J. Clin. Nutr. 2006, 84:471-472.
101. Levine M., Conry-Cantilena C., Wang Y., Welch R.W., Washko P.W., Dhariwal K.R., Park J.B., Lazarev A., Graumlich J., King J., Cantilena L.R. Vitamin C pharmacokinetics in healthy volunteers: evidence for a recommended dietary allowance. Proc. Natl. Acad. Sci. U. S. A. 1996, 93:3704-3709.
102. Burri B.J., Jacob R.A. Human metabolism and the requirement for vitamin C. Vitamin C in Health and Disease 1997, 341-366. Marcel Dekker, New York. L. Packer, J. Fuchs (Eds.).
103. Ames B.N. Low micronutrient intake may accelerate the degenerative diseases of aging through allocation of scarce micronutrients by triage. Proc. Natl. Acad. Sci. U. S. A. 2006, 103:17589-17594.
104. Levine M., Eck P. Vitamin C: working on the x-axis. Am. J. Clin. Nutr. 2009, 90:1121-1123.
105. Ito A., Hayashi S.-i., Yoshida T. Participation of a cytochrome b5-like hemoprotein of outer mitochondrial membrane (OM cytochrome b) in NADH-semidehydroascorbic acid reductase activity of rat liver. Biochem. Biophys. Res. Commun. 1981, 101:591-598.
106. Borgese N., Pietrini G. Distribution of the integral membrane protein NADH-cytochrome b5 reductase in rat liver cells, studied with a quantitative radioimmunoblotting assay. Biochem. J. 1986, 239:393-403.
107. May J.M., Qu Z., Cobb C.E. Recycling of the ascorbate free radical by human erythrocyte membranes. Free Radic. Biol. Med. 2001, 31:117-124.
108. Bode A.M., Cunningham L., Rose R.C. Spontaneous decay of oxidized ascorbic acid (dehydro-l-ascorbic acid) evaluated by high-pressure liquid chromatography. Clin. Chem. 1990, 36:1807-1809.
109. Borsook H., Davenport H.W., Jeffreys C.E.P., Warner R.C. The oxidation of ascorbic acid and its reduction in vitro and in vivo. J. Biol. Chem. 1937, 117:237-279.
110. Bogdanski K., Bogdanska H. Sur la stabilite de l'acide l-dehdroascorbique dans les solutions cbeaqueses. Bull. Acad. Pol. Sci. 1955, 3:41-44.
111. Winkler B.S., Orselli S.M., Rex T.S. The redox couple between glutathione and ascorbic acid: a chemical and physiological perspective. Free Radic. Biol. Med. 1994, 17:333-349.
112. Wells W.W., Xu D.P., Yang Y.F., Rocque P.A. Mammalian thioltransferase (glutaredoxin) and protein disulfide isomerase have dehydroascorbate reductase activity. J. Biol. Chem. 1990, 265:15361-15364.
113. May J.M., Mendiratta S., Hill K.E., Burk R.F. Reduction of dehydroascorbate to ascorbate by the selenoenzyme thioredoxin reductase. J. Biol. Chem. 1997, 272:22607-22610.
114. Del Bello B., Maellaro E., Sugherini L., Santucci A., Comporti M., Casini A.F. Purification of NADPH-dependent dehydroascorbate reductase from rat liver and its identification with 3 alpha-hydroxysteroid dehydrogenase. Biochem. J. 1994, 304:385-390.
115. Frei B., England L., Ames B.N. Ascorbate is an outstanding antioxidant in human blood plasma. Proc. Natl. Acad. Sci. U. S. A. 1989, 86:6377-6381.
116. Linster C.L., Van Schaftingen E. Vitamin C. Biosynthesis, recycling and degradation in mammals. FEBS J. 2007, 274:1-22.
117. Corti A., Casini A.F., Pompella A. Cellular pathways for transport and efflux of ascorbate and dehydroascorbate. Arch. Biochem. Biophys. 2010, 500:107-115.
118. Bielski B.H.J., Allen A.O., Schwart H.A. Mechanism of disproportionation of ascorbate radicals. J. Am. Chem. Soc. 1981, 103:3516-3518.
119. Niki E., Noguchi N. Protection of human low-density lipoprotein from oxidative modification by vitamin C. Vitamin C in Health and Disease 1997, 183-192. Marcel Dekker, New York. L. Packer, J. Fuchs (Eds.).
120. Lynch S.M., Morrow J.D., Roberts L.J., Frei B. Formation of non-cyclooxygenase-derived prostanoids (F2-isoprostanes) in plasma and low density lipoprotein exposed to oxidative stress in vitro. J. Clin. Invest. 1994, 93:998-1004.
121. Golumbic C., Mattill H.A. Antioxidants and the autoxidation of fats. XIII. The antioxygenic action of ascorbic acid in association with tocopherols, hydroquinones and related compounds. J. Am. Chem. Soc. 1941, 63:1279-1280.
122. Burton G.W., Ingold K.U. Vitamin E: application of the principles of physical organic chemistry to the exploration of its structure and function. Acc. Chem. Res. 1986, 19:194-201.
123. Csallany A.S., Draper H.H., Shah S.N. Conversion of d-alpha-tocopherol-C14 to tocopheryl-p-quinone in vivo. Arch. Biochem. Biophys. 1962, 98:142-145.
124. Bruno R.S., Leonard S.W., Atkinson J., Montine T.J., Ramakrishnan R., Bray T.M., Traber M.G. Faster plasma vitamin E disappearance in smokers is normalized by vitamin C supplementation. Free Radic. Biol. Med. 2006, 40:689-697.
125. Berger T.M., Polidori M.C., Dabbagh A., Evans P.J., Halliwell B., Morrow J.D., Roberts L.J., Frei B. Antioxidant activity of vitamin C in iron-overloaded human plasma. J. Biol. Chem. 1997, 272:15656-15660.
126. Suh J., Zhu B.-Z., Frei B. Ascorbate does not act as a pro-oxidant towards lipids and proteins in human plasma exposed to redox-active transition metal ions and hydrogen peroxide. Free Radic. Biol. Med. 2003, 34:1306-1314.
127. Chen K., Suh J., Carr A.C., Morrow J.D., Zeind J., Frei B. Vitamin C suppresses oxidative lipid damage in vivo, even in the presence of iron overload. Am. J. Physiol. Endocrinol. Metab. 2000, 279:E1406-E1412.
128. Halliwell B. Vitamin C: poison, prophylactic or panacea?. Trends Biochem. Sci. 1999, 24:255-259.
129. Frei B., Lawson S. Vitamin C and cancer revisited. Proc. Natl. Acad. Sci. U. S. A. 1998, 105:11037-11038.
130. Rees S., Slater T.F. Ascorbic acid and lipid peroxidation: the cross-over effect. Acta Biochim. Biophys. Hung. 1987, 22:241-249.
131. Buettner G.R., Jurkiewicz B.A. Chemistry and biochemistry of ascorbic acid. Handbook of Antioxidants 1996, 91-115. Marcel Dekker, New York. E. Cadenas, L. Packer (Eds.).
132. Wang W., Knovich M.A., Coffman L.G., Torti F.M., Torti S.V. Serum ferritin: past, present and future. Biochim. Biophys. Acta - Gen. Subj. 2010, 1800:760-769.
133. Richardson D.R., Ponka P. The molecular mechanisms of the metabolism and transport of iron in normal and neoplastic cells. Biochim. Biophys. Acta Rev. Biomembr. 1997, 1331:1-40.
134. Buettner G.R. The reaction of superoxide, formate radical, and hydrated electron with transferrin and its model compound, Fe(III)-ethylenediamine-N,N'-bis[2-(2-hydroxyphenyl) acetic acid] as studied by pulse radiolysis. J. Biol. Chem. 1987, 262:11995-11998.
135. Sirivech S., Frieden E., Osaki S. The release of iron from horse spleen ferritin by reduced flavins. Biochem. J. 1974, 143:311-315.
136. Boyer R.F., MacCleary C.J. Superoxide ion as a primary reductant in ascorbate-mediated ferritin iron release. Free Radic. Biol. Med. 1987, 3:389-395.
137. Keyer K., Imlay J.A. Superoxide accelerates DNA damage by elevating free-iron levels. Proc. Natl. Acad. Sci. U. S. A. 1996, 93:13635-13640.
138. Biemond P., van Eijk H.G., Swaak A.J., Koster J.F. Iron mobilization from ferritin by superoxide derived from stimulated polymorphonuclear leukocytes. Possible mechanism in inflammation diseases. J. Clin. Invest. 1984, 73:1576-1579.
139. Coudray C., Pucheu S., Boucher F., Arnaud J., de Leiris J., Favier A. Effect of ischemia/reperfusion sequence on cytosolic iron status and its release in the coronary effluent in isolated rat hearts. Biol. Trace Elem. Res. 1994, 41:69-75.
140. Bailey D.M., Raman S., McEneny J., Young I.S., Parham K.L., Hullin D.A., Davies B., McKeeman G., McCord J.M., Lewis M.H. Vitamin C prophylaxis promotes oxidative lipid damage during surgical ischemia-reperfusion. Free Radic. Biol. Med. 2006, 40:591-600.
141. Buettner G.R., Chamulitrat W. The catalytic activity of iron in synovial fluid as monitored by the ascorbate free radical. Free Radic. Biol. Med. 1990, 8:55-56.
142. Dabbagh A.J., Trenam C.W., Morris C.J., Blake D.R. Iron in joint inflammation. Ann. Rheum. Dis. 1993, 52:67-73.
143. Galley H.F., Davies M.J., Webster N.R. Ascorbyl radical formation in patients with sepsis: effect of ascorbate loading. Free Radic. Biol. Med. 1996, 20:139-143.
144. Güner G., Kirkali G., Yenisey Ç., Töre R. Cytosol and serum ferritin in breast carcinoma. Cancer Lett. 1992, 67:103-112.
145. Miyata Y., Koga S., Nishikido M., Hayashi T., Kanetake H. Relationship between serum ferritin levels and tumour status in patients with renal cell carcinoma. BJU Int. 2001, 88:974-977.
146. Basso D., Fabris C., Del Pavero G., Meggiato T., Panozzo M.P., Vianello D., Plebani M., Maccarato R. Hepatic changes and serum ferritin in pancreatic cancer and other gastrointestinal diseases: the role of cholestasis. Ann. Clin. Biochem. 1991, 28:34-38.
147. Hann H.W., Lange B., Stahlhut M.W., McGlynn K.A. Prognostic importance of serum transferrin and ferritin in childhood Hodgkin's disease. Cancer 1990, 66:313-316.
148. Jacobs A. Serum ferritin and malignant tumours. Med. Oncol. Tumor Pharmacother. 1984, 1:149-156.
149. Feng D., Nagy J.A., Dvorak A.M., Dvorak H.F. Different pathways of macromolecule extravasation from hyperpermeable tumor vessels. Microvasc. Res. 2000, 59:24-37.
150. Rossiello R., Carriero M.V., Giordano G.G. Distribution of ferritin, transferrin and lactoferrin in breast carcinoma tissue. J. Clin. Pathol. 1984, 37:51-55.
151. 2-mediated cytotoxicity of pharmacologic ascorbate concentrations to neuroblastoma cells: potential role of lactate and ferritin. Cell. Physiol. Biochem. 2010, 25:767-774.
152. Rousseau I., Puntarulo S. Ferritin-dependent radical generation in rat liver homogenates. Toxicology 2009, 264:155-161.
153. Baader S.L., Bill E., Trautwein A.X., Bruchelt G., Matzanke B.F. Mobilization of iron from cellular ferritin by ascorbic acid in neuroblastoma SK-N-SH cells: an EPR study. FEBS Lett. 1996, 381:131-134.
154. Olakanmi O., Stokes J.B., Britigan B.E. Acquisition of iron bound to low molecular weight chelates by human monocyte-derived macrophages. J. Immunol. 1994, 153:2691-2703.
155. Cameron E., Campbell A. The orthomolecular treatment of cancer. II. Clinical trial of high-dose ascorbic acid supplements in advanced human cancer. Chem. Biol. Interact. 1974, 9:285-315.
156. Cameron E., Campbell A., Jack T. The orthomolecular treatment of cancer. III. Reticulum cell sarcoma: double complete regression induced by high-dose ascorbic acid therapy. Chem. Biol. Interact. 1975, 11:387-393.
157. Cameron E., Pauling L. Supplemental ascorbate in the supportive treatment of cancer: prolongation of survival times in terminal human cancer. Proc. Natl. Acad. Sci. U. S. A. 1976, 73:3685-3689.
158. Cameron E., Pauling L. Supplemental ascorbate in the supportive treatment of cancer: reevaluation of prolongation of survival times in terminal human cancer. Proc. Natl. Acad. Sci. U. S. A. 1978, 75:4538-4542.
159. Creagan E.T., Moertel C.G., O'Fallon J.R., Schutt A.J., O'Connell M.J., Rubin J., Frytak S. Failure of high-dose vitamin C (ascorbic acid) therapy to benefit patients with advanced cancer. A controlled trial. N. Engl. J. Med. 1979, 301:687-690.
160. Moertel C.G., Fleming T.R., Creagan E.T., Rubin J., O'Connell M.J., Ames M.M. High-dose vitamin C versus placebo in the treatment of patients with advanced cancer who have had no prior chemotherapy. A randomized double-blind comparison. N. Engl. J. Med. 1985, 312:137-141.
161. Drisko J.A., Chapman J., Hunter V.J. The use of antioxidants with first-line chemotherapy in two cases of ovarian cancer. J. Am. Coll. Nutr. 2003, 22:118-123.
162. Riordan H.D., Casciari J.J., Gonzalez M.J., Riordan N.H., Miranda-Massari J.R., Taylor P., Jackson J.A. A pilot clinical study of continuous intravenous ascorbate in terminal cancer patients. P. R. Health Sci. J. 2005, 24:269-276.
163. Sestili P., Brandi G., Brambilla L., Cattabeni F., Cantoni O. Hydrogen peroxide mediates the killing of U937 tumor cells elicited by pharmacologically attainable concentrations of ascorbic acid: cell death prevention by extracellular catalase or catalase from cocultured erythrocytes or fibroblasts. J. Pharmacol. Exp. Ther. 1996, 277:1719-1725.
164. Verrax J., Calderon P.B. Pharmacologic concentrations of ascorbate are achieved by parenteral administration and exhibit antitumoral effects. Free Radic. Biol. Med. 2009, 47:32-40.
165. Clement M.V., Ramalingam J., Long L.H., Halliwell B. The in vitro cytotoxicity of ascorbate depends on the culture medium used to perform the assay and involves hydrogen peroxide. Antioxid. Redox Signal. 2001, 3:157-163.
166. Wagner B.A., Teesch L.M., Buettner G.R., Britigan B.E., Burns C.P., Reszka K.J. Inactivation of anthracyclines by serum heme proteins. Chem. Res. Toxicol. 2007, 20:920-926.
167. Giandomenico A.R., Cerniglia G.E., Biaglow J.E., Stevens C.W., Koch C.J. The importance of sodium pyruvate in assessing damage produced by hydrogen peroxide. Free Radic. Biol. Med. 1997, 23:426-434.
168. Long L.H., Halliwell B. Artefacts in cell culture: pyruvate as a scavenger of hydrogen peroxide generated by ascorbate or epigallocatechin gallate in cell culture media. Biochem. Biophys. Res. Commun. 2009, 388:700-704.
169. Casciari J.J., Riordan N.H., Schmidt T.L., Meng X.L., Jackson J.A., Riordan H.D. Cytotoxicity of ascorbate, lipoic acid, and other antioxidants in hollow fibre in vitro tumours. Br. J. Cancer 2001, 84:1544-1550.
170. Radi R., Turrens J.F., Chang L.Y., Bush K.M., Crapo J.D., Freeman B.A. Detection of catalase in rat heart mitochondria. J. Biol. Chem. 1991, 266:22028-22034.
171. Benade L., Howard T., Burk D. Synergistic killing of Ehrlich ascites carcinoma cells by ascorbate and 3-amino-1,2,4,-triazole. Oncology 1969, 23:33-43.
172. Gaetani G.F., Galiano S., Canepa L., Ferraris A.M., Kirkman H.N. Catalase and glutathione peroxidase are equally active in detoxification of hydrogen peroxide in human erythrocytes. Blood 1989, 73:334-339.
173. Gaetani G.F., Kirkman H.N., Mangerini R., Ferraris A.M. Importance of catalase in the disposal of hydrogen peroxide within human erythrocytes. Blood 1994, 84:325-330.
174. 2 and GPx concentrations. Free. Radic. Res. 2007, 41:1201-1211.
175. Sasaki K., Bannai S., Makino N. Kinetics of hydrogen peroxide elimination by human umbilical vein endothelial cells in culture. Biochim. Biophys. Acta Gen. Subj. 1998, 1380:275-288.
176. Low F.M., Hampton M.B., Winterbourn C.C. Peroxiredoxin 2 and peroxide metabolism in the erythrocyte. Antioxid. Redox Signal. 2008, 10:1621-1630.
177. 2 is not reflected in its reaction with other oxidants and thiol reagents. J. Biol. Chem. 2007, 282:11885-11892.
178. Chance B., Sies H., Boveris A. Hydroperoxide metabolism in mammalian organs. Physiol. Rev. 1979, 59:527-605.
179. Schafer F.Q., Buettner G.R. Redox environment of the cell as viewed through the redox state of the glutathione disulfide/glutathione couple. Free Radic. Biol. Med. 2001, 30:1191-1212.
180. Liu J., Hinkhouse M.M., Sun W., Weydert C.J., Ritchie J.M., Oberley L.W., Cullen J.J. Redox regulation of pancreatic cancer cell growth: role of glutathione peroxidase in the suppression of the malignant phenotype. Hum. Gene Ther. 2004, 15:239-250.
181. Oberley L.W. Mechanism of the tumor suppressive effect of MnSOD overexpression. Biomed. Pharmacother. 2005, 59:143-148.
182. Glickstein H., Ben El R., Shvartsman M., Cabantchik Z.I. Intracellular labile iron pools as direct targets of iron chelators: a fluorescence study of chelator action in living cells. Blood 2005, 106:3242-3250.
183. Browne P., Shalev O., Hebbel R.P. The molecular pathobiology of cell membrane iron: the sickle red cell as a model. Free Radic. Biol. Med. 1998, 24:1040-1048.
184. Hempel S.L., Buettner G.R., Wessels D.A., Galvan G.M., O'Malley Y.Q. Extracellular Iron(II) can protect cells from hydrogen peroxide. Arch. Biochem. Biophys. 1996, 330:401-408.
185. Schafer F.Q., Qian S.Y., Buettner G.R. Iron and free radical oxidations in cell membranes. Cell. Mol. Biol. (Noisy-le-grand) 2000, 46:657-662.
186. Jurkiewicz B.A., Buettner G.R. EPR detection of free radicals in UV-irradiated skin: mouse versus human. Photochem. Photobiol. 1996, 64.
187. Bloomer S.A., Brown K.E., Buettner G.R., Kregel K.C. Dysregulation of hepatic iron with aging: implications for heat stress-induced oxidative liver injury. Am. J. Physiol. Regul. Integr. Comp. Physiol. 2008, 294:R1165-R1174.
188. Spencer K.T., Lindower P.D., Buettner G.R., Kerber R.E. Transition metal chelators reduce directly measured myocardial free radical production during reperfusion. J. Cardiovas. Pharmacol. 1998, 32:343-348.
189. Reif D.W. Ferritin as a source of iron for oxidative damage. Free Radic. Biol. Med. 1992, 12:417-427.
190. Carmine T.C., Evans P., Bruchelt G., Evans R., Handgretinger R., Niethammer D., Halliwell B. Presence of iron catalytic for free radical reactions in patients undergoing chemotherapy: implications for therapeutic management. Cancer Lett. 1995, 94:219-226.
191. Persson H.L. Radiation-induced lysosomal iron reactivity: implications for radioprotective therapy. IUBMB Life 2006, 58:395-401.
192. Buettner G.R. Ascorbate autoxidation in the presence of iron and copper chelates. Free. Radic. Res. Commun. 1986, 1:349-353.
193. Miller D.M., Buettner G.R., Aust S.D. Transition metals as catalysts of "autoxidation" reactions. Free Radic. Biol. Med. 1990, 8:95-108.
194. Kimoto E., Tanaka H., Gyotoku J., Morishige F., Pauling L. Enhancement of antitumor activity of ascorbate against Ehrlich ascites tumor cells by the copper:glycylglycylhistidine complex. Cancer Res. 1983, 43:824-828.
195. Batinić-Haberle I., Rebouças J.S., Spasojević I. Superoxide dismutase mimics: chemistry, pharmacology, and therapeutic potential. Antioxid. Redox Signal. 2010, 13:877-918.
196. Gardner P.R., Nguyen D.-D.H., White C.W. Superoxide scavenging by Mn(II/III) tetrakis (1-Methyl-4-pyridyl) porphyrin in mammalian cells. Arch. Biochem. Biophys. 1996, 325:20-28.
197. Zhong W., Yan T., Webber M.M., Oberley T.D. Alteration of cellular phenotype and responses to oxidative stress by manganese superoxide dismutase and a superoxide dismutase mimic in RWPE-2 human prostate adenocarcinoma cells. Antioxid. Redox Signal. 2004, 6:513-522.
198. Tian J., Peehl D.M., Knox S.J. Metalloporphyrin synergizes with ascorbic acid to inhibit cancer cell growth through Fenton chemistry. Cancer Biother. Radiopharm. 2010, 25:439-448.
199. Batinic-Haberle I., Rajic Z., Tovmasyan A., Reboucas J.S., Ye X., Leong K.W., Dewhirst M.W., Vujaskovic Z., Benov L., Spasojevic I. Diverse functions of cationic Mn(III) N-substituted pyridylporphyrins, recognized as SOD mimics. Free Radic. Biol. Med. 2011, 51:1035-1053.
200. Ye X., Fels D., Tovmasyan A., Aird K.M., Dedeugd C., Allensworth J.L., Kos I., Park W., Spasojevic I., Devi G.R., Dewhirst M.W., Leong K.W., Batinic-Haberle I. Cytotoxic effects of Mn(III) N-alkylpyridylporphyrins in the presence of cellular reductant, ascorbate. Free. Radic. Res. 2011, 45:1289-1306.
201. Klockars M., Weber T., Tanner P., Hellstrom P.E., Pettersson T. Pleural fluid ferritin concentrations in human disease. J. Clin. Pathol. 1985, 38:818-824.
202. Weinberger A., Simkin P. Plasma proteins in synovial fluids of normal human joints. Semin. Arthritis Rheum. 1989, 19:66-76.
203. Halliwell B. Oxygen radicals, nitric oxide and human inflammatory joint disease. Ann. Rheum. Dis. 1995, 54:505-510.
204. Baronzio G., Schwartz L., Kiselevsky M., Guais A., Sanders E., Milanesi G., Baronzio M., Freitas I. Tumor interstitial fluid as modulator of cancer inflammation, thrombosis, immunity and angiogenesis. Anticancer. Res. 2012, 32:405-414.
205. Nagy J.A., Masse E.M., Herzberg K.T., Meyers M.S., Yeo K.-T., Yeo T.-K., Sioussat T.M., Dvorak H.F. Pathogenesis of ascites tumor growth: vascular permeability factor, vascular hyperpermeability, and ascites fluid accumulation. Cancer Res. 1995, 55:360-368.
206. Nagy J.A., Herzberg K.T., Dvorak J.M., Dvorak H.F. Pathogenesis of malignant ascites formation: initiating events that lead to fluid accumulation. Cancer Res. 1993, 53:2631-2643.
207. Roche M., Rondeau P., Singh N.R., Tarnus E., Bourdon E. The antioxidant properties of serum albumin. FEBS Lett. 2008, 582:1783-1787.
208. Halliwell B., Gutteridge J.M.C. The antioxidants of human extracellular fluids. Arch. Biochem. Biophys. 1990, 280:1-8.
209. Espey M.G., Chen P., Chalmers B., Drisko J., Sun A.Y., Levine M., Chen Q. Pharmacologic ascorbate synergizes with gemcitabine in preclinical models of pancreatic cancer. Free Radic. Biol. Med. 2011, 50:1610-1619.
210. Riordan N.H., Riordan H.D., Meng X., Jackson J.A. Intravenous ascorbate as a tumor cytotoxic chemotherapeutic agent. Med. Hypotheses 1995, 44:207-213.
211. Riordan H.D., Riordan N.H., Jackson J.A., Casciari J.J., Hunninghake R., Gonzalez M.J., Mora E.M., Miranda-Massari J.R., Roscario N. Intravenous vitamin C as a chemotherapy agent: a report on clinical cases. P. R. Health Sci. J. 2004, 23:115-118.
212. Padayatty S.J., Riordan H.D., Hewitt S.M., Katz A., Hoffer L.J., Levine M. Intravenously administered vitamin C as cancer therapy: three cases. CMAJ 2006, 174:937-942.
213. Padayatty S.J., Sun A.Y., Chen Q., Espey M.G., Drisko J., Levine M. Vitamin C: intravenous use by complementary and alternative medicine practitioners and adverse effects. PLoS One 2010, 5:e11414.
214. Tian W.N., Braunstein L.D., Apse K., Pang J., Rose M., Tian X., Stanton R.C. Importance of glucose-6-phosphate dehydrogenase activity in cell death. Am. J. Physiol. 1999, 276:C1121-C1131.
215. Campbell G.D., Steinberg M.H., Bower J.D. Letter: Ascorbic acid-induced hemolysis in G-6-PD deficiency. Ann. Intern. Med. 1975, 82:810-815.
216. Mehta J.B., Singhal S.B., Mehta B.C. Ascorbic-acid-induced haemolysis in G-6-PD deficiency. Lancet 1990, 336:944.
217. Rees D.C., Kelsey H., Richards J.D. Acute haemolysis induced by high dose ascorbic acid in glucose-6-phosphate dehydrogenase deficiency. BMJ 1993, 306:841-842.
218. Wong K., Thomson C., Bailey R.R., McDiarmid S., Gardner J. Acute oxalate nephropathy after a massive intravenous dose of vitamin C. Aust. N. Z. J. Med. 1994, 24:410-411.
219. Campbell A., Jack T. Acute reactions to mega ascorbic acid therapy in malignant disease. Scott. Med. J. 1979, 24:151-153.
220. Hoffer L.J., Levine M., Assouline S., Melnychuk D., Padayatty S.J., Rosadiule K., Rousseau C., Robitaille L., Miller W.H.J. Phase I clinical trial of i.v. ascorbic acid in advanced malignancy. Ann. Oncol. 2008, 19:1969-1974.
221. Monti D.A., Mitchell E., Bazzan A.J., Littman S., Zabrecky G., Yeo C.J., Pillai M.V., Newberg A.B., Deshmukh S., Levine M. Phase I evaluation of intravenous ascorbic acid in combination with gemcitabine and erlotinib in patients with metastatic pancreatic cancer. PLoS One 2012, 7:e29794.
222. Prasad K.N., Sinha P.K., Ramanujam M., Sakamoto A. Sodium ascorbate potentiates the growth inhibitory effect of certain agents on neuroblastoma cells in culture. Proc. Natl. Acad. Sci. U. S. A. 1979, 76:829-832.
223. Kurbacher C.M., Wagner U., Kolster B., Andretti P.E., Krebs D., Bruckner H.W. Ascorbic acid (vitamin C) improves the antineoplastic activity of doxorubicin, cisplatin, and paclitaxel in human breast carcinoma cells in vitro. Cancer Lett. 1996, 103:183-189.
224. Herst P.M., Broadley K.W.R., Harper J.L., McConnell M.J. Pharmacological concentrations of ascorbate radiosensitize glioblastoma multiforme primary cells by increasing oxidative DNA damage and inhibiting G2/M arrest. Free Radic. Biol. Med. 2012, 52:1486-1493.
225. Vollbracht C., Schneider B., Leendert V., Weiss G., Auerbach L., Beuth J. Intravenous vitamin C administration improves quality of life in breast cancer patients during chemo-/radiotherapy and aftercare: results of a retrospective, multicentre, epidemiological cohort study in Germany. In Vivo 2011, 25:983-990.
226. Terpstra M., Ugurbil K., Tkac I. Noninvasive quantification of human brain ascorbate concentration using 1H NMR spectroscopy at 7 T. NMR Biomed. 2010, 23:227-232.
227. Terpstra M., Torkelson C., Emir U., Hodges J.S., Raatz S. Noninvasive quantification of human brain antioxidant concentrations after an intravenous bolus of vitamin C. NMR Biomed. 2011, 24:521-528.
228. Omaye S.T., Skala J.H., Jacob R.A. Rebound effect with ascorbic acid in adult males. Am. J. Clin. Nutr. 1988, 48:379-380.
229. Tsao C.S., Leung P.Y. Urinary ascorbic acid levels following the withdrawal of large doses of ascorbic acid in guinea pigs. J. Nutr. 1988, 118:895-900.
230. Morrow J.D., Hill K.E., Burk R.F., Nammour T.M., Badr K.F., Roberts L.J. A series of prostaglandin F2-like compounds are produced in vivo in humans by a non-cyclooxygenase, free radical-catalyzed mechanism. Proc. Natl. Acad. Sci. U. S. A. 1990, 87:9383-9387.
231. Milne G.L., Sanchez S.C., Musiek E.S., Morrow J.D. Quantification of F2-isoprostanes as a biomarker of oxidative stress. Nat. Protoc. 2007, 2:221-226.
232. Kadiiska M.B., Gladen B.C., Baird D.D., Germolec D., Graham L.B., Parker C.E., Nyska A., Wachsman J.T., Ames B.N., Basu S., Brot N., FitzGerald G.A., Floyd R.A., George M., Heinecke J.W., Hatch G.E., Hensley K., Lawson J.A., Marnett L.J., Morrow J.D., Murray D.M., Plastaras J., Roberts L.J., Rokach J., Shigenaga M.K., Sohal R.S., Sun J., Tice R.R., Van Thiel D.H., Wellner D., Walter P.B., Tomer K.B., Mason R.P., Barrett J.C. Biomarkers of oxidative stress study II: are oxidation products of lipids, proteins, and DNA markers of CCl4 poisoning?. Free Radic. Biol. Med. 2005, 38:698-710.
233. Levine M., Padayatty S.J., Espey M.G. Vitamin C: a concentration-function approach yields pharmacology and therapeutic discoveries. Adv. Nutr. 2011, 2:78-88.
234. Emir U.E., Raatz S., McPherson S., Hodges J.S., Torkelson C., Tawfik P., White T., Terpstra M. Noninvasive quantification of ascorbate and glutathione concentration in the elderly human brain. NMR Biomed. 2011, 24:888-894.
235. Lönnrot K., MetsÄ-KetelÄ T., Molnár G., Ahonen J.-P., Latvala M., Peltola J., PietilÄ T., Alho H. The effect of ascorbate and ubiquinone supplementation on plasma and CSF total antioxidant capacity. Free Radic. Biol. Med. 1996, 21:211-217.
236. Bayir H., Kagan V.E., Tyurina Y.Y., Tyurin V., Ruppel R.A., Adelson P.D., Graham S.H., Janesko K., Clark R.S., Kochanek P.M. Assessment of antioxidant reserves and oxidative stress in cerebrospinal fluid after severe traumatic brain injury in infants and children. Pediatr. Res. 2002, 51:571-578.
237. Voigt K., Kontush A., Stuerenburg H.J., Muench-Harrach D., Hansen H.C., Kunze K. Decreased plasma and cerebrospinal fluid ascorbate levels in patients with septic encephalopathy. Free. Radic. Res. 2002, 36:735-739.
238. Harrison F.E., May J.M. Vitamin C function in the brain: vital role of the ascorbate transporter SVCT2. Free Radic. Biol. Med. 2009, 46:719-730.
239. Vissers M.C.M., Gunningham S.P., Morrison M.J., Dachs G.U., Currie M.J. Modulation of hypoxia-inducible factor-1 alpha in cultured primary cells by intracellular ascorbate. Free Radic. Biol. Med. 2007, 42:765-772.
240. Koh W.S., Choi W.H., Lee S.J., Park C.S., Park C.H. Enhancement of plasmacytoma cell growth by ascorbic acid is mediated via glucose 6-phosphate dehydrogenase. Cancer Res. Treat. 2007, 39:22-29.
241. Castranova V., Wright J.R., Colby H.D., Miles P.R. Ascorbate uptake by isolated rat alveolar macrophages and type II cells. J. Appl. Physiol. 1983, 54:208-214.
242. Korcok J., Dixon S.J., Lo T.C.Y., Wilson J.X. Differential effects of glucose on dehydroascorbic acid transport and intracellular ascorbate accumulation in astrocytes and skeletal myocytes. Brain Res. 2003, 993:201-207.
243. Bergsten P., Yu R., Kehrl J., Levine M. Ascorbic acid transport and distribution in human B lymphocytes. Arch. Biochem. Biophys. 1995, 317:208-214.
244. May J.M., Qu Z.-C. Chelation of intracellular iron enhances endothelial barrier function: a role for vitamin C?. Arch. Biochem. Biophys. 2010, 500:162-168.
245. Reidling J.C., Subramanian V.S., Dahhan T., Sadat M., Said H.M. Mechanisms and regulation of vitamin C uptake: studies of the hSVCT systems in human liver epithelial cells. Am. J. Physiol. Gastrointest. Liver Physiol. 2008, 295:G1217-G1227.
246. Kramarenko G.G., Wilke W.W., Dayal D., Buettner G.R., Schafer F.Q. Ascorbate enhances the toxicity of the photodynamic action of Verteporfin in HL-60 cells. Free Radic. Biol. Med. 2006, 40:1615-1627.
247. Steffner R.J., Wu L., Powers A.C., May J.M. Ascorbic acid recycling by cultured β cells: effects of increased glucose metabolism. Free Radic. Biol. Med. 2004, 37:1612-1621.
248. May J.M., Qu Z.-C. Ascorbate-dependent electron transfer across the human erythrocyte membrane. Biochim. Biophys. Acta Biomembr. 1999, 1421:19-31.
249. Han M., Pendem S., Teh S.L., Sukumaran D.K., Wu F., Wilson J.X. Ascorbate protects endothelial barrier function during septic insult: role of protein phosphatase type 2A. Free Radic. Biol. Med. 2010, 48:128-135.
250. May J., Li L., Hayslett K., Qu Z.-c. Ascorbate transport and recycling by SH-SY5Y neuroblastoma cells: response to glutamate toxicity. Neurochem. Res. 2006, 31:785-794.
251. 2 and transition metal ions in the genotoxic action of ascorbic acid in cell culture models. Toxicol. Lett. 2007, 170:57-65.
252. Peterkofsky B., Prather W. Cytotoxicity of ascorbate and other reducing agents towards cultured fibroblasts as a result of hydrogen peroxide formation. J. Cell. Physiol. 1977, 90:61-70.
253. Johnson N.A., Chen B.-H., Sung S.-Y., Liao C.-H., Hsiao W.-C., Chung L.W.K., Hsieh C.-L. A novel targeting modality for renal cell carcinoma: human osteocalcin promoter-mediated gene therapy synergistically induced by vitamin C and vitamin D3. J. Gene Med. 2010, 12:892-903.
254. Park C.H., Amare M., Savin M.A. Growth suppression of human leukemic cells in vitro by l-ascorbic acid. Cancer Res. 1980, 40:1062-1065.
255. Jamison J.M., Gilloteaux J., Nassiri M.R., Venugopal M., Neal D.R., Summers J.L. Cell cycle arrest and autoschizis in a human bladder carcinoma cell line following vitamin C and vitamin K3 treatment. Biochem. Pharmacol. 2004, 67:337-351.
256. Rozanova N., Zhang J.Z., Heck D.E. Catalytic therapy of cancer with porphyrins and ascorbate. Cancer Lett. 2007, 252:216-224.
257. Berndt C., Kurz T., Bannenberg S., Jacob R., Holmgren A., Brunk U.T. Ascorbate and endocytosed Motexafin gadolinium induce lysosomal rupture. Cancer Lett. 2011, 307:119-123.
258. Solovieva M.E., Soloviev V.V., Akatov V.S. Vitamin B12b increases the cytotoxicity of short-time exposure to ascorbic acid, inducing oxidative burst and iron-dependent DNA damage. Euro. J. Phmacol. 2007, 566:206-214.
259. Biswas S., Zhao X., Mone A.P., Mo X., Vargo M., Jarjoura D., Byrd J.C., Muthusamy N. Arsenic trioxide and ascorbic acid demonstrate promising activity against primary human CLL cells in vitro. Leuk. Res. 2010, 34:925-931.
260. Hahm E., Jin D.-H., Kang J.S., Kim Y.-I., Hong S.-W., Lee S.K., Kim H.N., Jung D.J., Kim J.E., Shin D.H., Hwang Y.I., Kim Y.S., Hur D.Y., Yang Y., Cho D., Lee M.-S., Lee W.J. The molecular mechanisms of vitamin C on cell cycle regulation in B16F10 murine melanoma. J. Cell. Biochem. 2007, 102:1002-1010.
261. Josephy P.D., Palcic B., Skarsgard L.D. Ascorbate-enhanced cytotoxicity of misonidazole. Nature 1978, 271:370-372.
262. Belin S., Kaya F., Duisit G., Giacometti S., Ciccolini J., Fontes M. Antiproliferative effect of ascorbic acid is associated with the inhibition of genes necessary to cell cycle progression. PLoS One 2009, 4:e4409.
263. Verrax J., Stockis J., Tison A., Taper H.S., Calderon P.B. Oxidative stress by ascorbate/menadione association kills K562 human chronic myelogenous leukaemia cells and inhibits its tumour growth in nude mice. Biochem. Pharmacol. 2006, 72:671-680.
264. Ohtani S., Iwamaru A., Deng W., Ueda K., Wu G., Jayachandran G., Kondo S., Atkinson E.N., Minna J.D., Roth J.A., Ji L. Tumor suppressor 101F6 and ascorbate synergistically and selectively inhibit non-small cell lung cancer growth by caspase-independent apoptosis and autophagy. Cancer Res. 2007, 67:6293-6303.
265. Takemura Y., Satoh M., Satoh K., Hamada H., Sekido Y., Kubota S. High dose of ascorbic acid induces cell death in mesothelioma cells. Biochem. Biophys. Res. Commun. 2010, 394:249-253.
266. Yeom C.-H., Lee G., Park J.H., Yu J., Park S.I., Yi S.Y., Lee H.R., Hong Y.S., Yang J., Lee S. High dose concentration administration of ascorbic acid inhibits tumor growth in BALB/C mice implanted with sarcoma 180 cancer cells via the restriction of angiogenesis. J. Transl. Med. 2009, 7:70-79.
267. Park S., Ahn E.S., Lee S., Jung M., Park J.H., Yi S.Y., Yeom C.-H. Proteomic analysis reveals upregulation of RKIP in S-180 implanted BALB/C mouse after treatment with ascorbic acid. J. Cell. Biochem. 2009, 106:1136-1145.