High Concentrations of L-Ascorbic Acid Specifically Inhibit the Growth of Human Leukemic Cells via Downregulation of HIF-1α Transcription

PLoS ONE

Volumn 8, Issue 4, 2013, Pages

  Kawada, Hiroshi ^a   Kaneko, Mitsuyo ^a   Sawanobori, Masakazu ^a   Uno, Tomoko ^a   Matsuzawa, Hideyuki ^a   Nakamura, Yoshihiko ^a   Matsushita, Hiromichi ^a   Ando, Kiyoshi ^a  

^a TOKAI UNIVERSITY SCHOOL OF MEDICINE   (Japan)

Author keywords

[No Author keywords available]

Indexed keywords

ASCORBIC ACID; HYDROGEN PEROXIDE; HYPOXIA INDUCIBLE FACTOR 1ALPHA; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; PROTEIN BCL 2; PROTEIN BCL XL; PROTEIN MCL 1; VASCULOTROPIN; ANTINEOPLASTIC AGENT;

ANGIOGENESIS; ANIMAL EXPERIMENT; ANIMAL MODEL; ANTILEUKEMIC ACTIVITY; APOPTOSIS; ARTICLE; CANCER INHIBITION; CELL PROLIFERATION; CHRONIC MYELOID LEUKEMIA; CORRELATION ANALYSIS; DRUG ACTIVITY; DRUG EFFICACY; ENZYME REGULATION; ENZYME REPRESSION; GENE OVEREXPRESSION; GENE TRANSLOCATION; GENETIC TRANSCRIPTION; HEMATOPOIETIC STEM CELL; HIF 1A GENE; HUMAN; HUMAN CELL; IN VITRO STUDY; LEUKEMIA CELL; LYMPHATIC LEUKEMIA; MONOCYTIC LEUKEMIA; MOUSE; NONHUMAN; ONCOGENE; PROMYELOCYTIC LEUKEMIA; TREATMENT RESPONSE; VEGF GENE; ANIMAL; DISEASE COURSE; DISEASE MODEL; DRUG EFFECTS; DRUG SCREENING; GENE EXPRESSION REGULATION; GENETICS; K562 CELL LINE; LEUKEMIA; METABOLISM; PATHOLOGY; TOXICITY; TUMOR CELL LINE; TUMOR VOLUME;

MUS;

ANIMALS; ANTINEOPLASTIC AGENTS; ASCORBIC ACID; CELL LINE, TUMOR; CELL PROLIFERATION; DISEASE MODELS, ANIMAL; DISEASE PROGRESSION; GENE EXPRESSION REGULATION, LEUKEMIC; HEMATOPOIETIC STEM CELLS; HUMANS; HYPOXIA-INDUCIBLE FACTOR 1, ALPHA SUBUNIT; K562 CELLS; LEUKEMIA; MICE; TRANSCRIPTION, GENETIC; TUMOR BURDEN; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 84876515209     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0062717     Document Type: Article

References (63)

1. Cameron E, Pauling L, (1976) Supplemental ascorbate in the supportive treatment of cancer: Prolongation of survival times in terminal human cancer. Proc Natl Acad Sci USA 73: 3685-3689.
2. Cameron E, Pauling L, (1978) Supplemental ascorbate in the supportive treatment of cancer: reevaluation of prolongation of survival times in terminal human cancer. Proc Natl Acad Sci USA 75: 4538-4542.
3. Creagan ET, Moertel CG, O'Fallon JR, Schutt AJ, O'Connell MJ, et al. (1979) Failure of high-dose vitamin C (ascorbic acid) therapy to benefit patients with advanced cancer. A controlled trial. N Engl J Med 301: 687-690.
4. Moertel CG, Fleming TR, Creagan ET, Rubin J, O'Connell MJ, et al. (1985) 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 312: 137-141.
5. Padayatty SJ, Sun H, Wang Y, Riordan HD, Hewitt SM, et al. (2004) Vitamin C pharmacokinetics: implications for oral and intravenous use. Ann Intern Med 140: 533-537.
6. Chen Q, Espey MG, Sun AY, Pooput C, Kirk KL, 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.
7. Chen Q, Espey MG, Krishna MC, Mitchell JB, Corpe CP, et al. (2005) Pharmacologic ascorbic acid concentrations selectively kill cancer cells: action as a pro-drug to deliver hydrogen peroxide to tissues. Proc Natl Acad Sci USA 102: 13604-13609.
8. Padayatty SJ, Riordan HD, Hewitt SM, Katz A, Hoffer LJ, et al. (2006) Intravenously administered vitamin C as cancer therapy: three cases. CMAJ 174: 937-942.
9. Ohno S, Ohno Y, Suzuki N, Soma G, Inoue M, (2009) High-dose vitamin C (ascorbic acid) therapy in the treatment of patients with advanced cancer. Anticancer Res 29: 809-815.
10. Wang Y, Liu Y, Malek SN, Zheng P, Liu Y, (2011) Targeting HIF1α eliminates cancer stem cells in hematological malignancies. Cell Stem Cell 8: 399-411.
11. Deeb G, Vaughan MM, McInnis I, Ford LA, Sait SN, et al. (2011) Hypoxia-inducible factor-1α protein expression is associated with poor survival in normal karyotype adult acute myeloid leukemia. Leuk Res 35: 579-584.
12. Wellmann S, Guschmann M, Griethe W, Eckert C, von Stackelberg A, et al. (2004) Activation of the HIF pathway in childhood ALL, prognostic implications of VEGF. Leukemia 18: 926-933.
13. Abdel-Wahab O, Levine RL, (2010) Metabolism and the leukemic stem cell. J Exp Med 207: 677-680.
14. Piret JP, Minet E, Cosse JP, Ninane N, Debacq C, et al. (2005) Hypoxia-inducible factor-1-dependent overexpression of myeloid cell factor-1 protects hypoxic cells against tert-butyl hydroperoxide-induced apoptosis. J Biol Chem 280: 9336-9344.
15. Görlach A, Bonello S, (2008) The cross-talk between NF-kappaB and HIF-1: further evidence for a significant liaison. Biochem J 412: e17-19.
16. Semenza, G L (2000) HIF-1: mediator of physiological and pathophysiological responses to hypoxia. J Appl. Physiol 88, 1474-1480.
17. Maxwell PH (2005) Hypoxia-inducible factor as a physiological regulator. Exp Physiol 90, 791-797.
18. Ruas JL, Poellinger L (2005) Hypoxia-dependent activation of HIF into a ranscriptional regulator. Semin Cell Dev Biol 16, 514-522.
19. Myllyla R, Kuutti-Savolainen E-R, Kivirikko KI, (1978) The role of ascorbate in the prolyl hydroxylase reaction. Biochem Biophys Res Commun 83: 441-448.
20. de Jong L, Albracht SPJ, Kemp A, (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.
21. van Uden P, Kenneth NS, Rocha S (2008) Regulation of hypoxia-inducible factor-1α by NF-κB. Biochem J 412, 477-484.
22. Matsuo Y, MacLeod RA, Uphoff CC, Drexler HG, Nishizaki C, et al. (1997) Two acute monocytic leukemia (AML-M5a) cell lines (MOLM-13 and MOLM-14) with interclonal phenotypic heterogeneity showing MLL-AF9 fusion resulting from an occult chromosome insertion, ins(11;9)(q23;p22p23). Leukemia 11: 1469-1477.
23. Kawada H, Ando K, Tsuji T, Shimakura Y, Nakamura Y, et al. (1999) Rapid ex vivo expansion of human umbilical cord hematopoietic progenitors using a novel culture system. Exp Hematol 27: 904-915.
24. Riordan NH, Riordan HD, Meng X, Li Y, Jackson JA, (1995) Intravenous ascorbate as a tumor cytotoxic chemotherapeutic agent. Med Hypotheses 44: 207-213.
25. Chen Q, Espey MG, Sun AY, Lee JH, Krishna MC, et al. (2007) Ascorbate in pharmacologic concentrations selectively generates ascorbate radical and hydrogen peroxide in extracellular fluid in vivo. Proc Natl Acad Sci USA 104: 8749-8754.
26. Drisko JA, Chapman J, Hunter VJ, (2003) The use of antioxidants with first-line chemotherapy in two cases of ovarian cancer. J Am Coll Nutr 22: 118-123.
27. Kilkenny C, Browne WJ, Cuthill IC, Emerson M, Altman DG, (2010) Improving bioscience research reporting: the ARRIVE guidelines for reporting animal research. PLoS Biol 8: e1000412.
28. Cárcamo JM, Pedraza A, Bórquez-Ojeda O, Zhang B, Sanchez R, et al. (2004) Vitamin C is a kinase inhibitor: dehydroascorbic acid inhibits IκBα kinase β. Mol Cell Biol 24: 6645-6652.
29. Lin MT, Juan CY, Chang KJ, Chen WJ, Kuo ML, (2001) IL-6 inhibits apoptosis and retains oxidative DNA lesions in human gastric cancer AGS cells through up-regulation of anti-apoptotic gene mcl-1. Carcinogenesis 22: 1947-1953.
30. Chen N, Chen X, Huang R, Zeng H, Gong J, et al. (2009) BCL-xL is a target gene regulated by hypoxia-inducible factor-1α. J Biol Chem 284: 10004-10012.
31. Sasabe E, Tatemoto Y, Li D, Yamamoto T, Osaki T, (2005) Mechanism of HIF-1alpha-dependent suppression of hypoxia-induced apoptosis in squamous cell carcinoma cells. Cancer Sci 96: 394-402.
32. Yang CC, Lin LC, Wu MS, Chien CT, Lai MK, (2009) Repetitive hypoxic preconditioning attenuates renal ischemia/reperfusion induced oxidative injury via upregulating HIF-1 alpha-dependent bcl-2 signaling. Transplantation 88: 1251-1260.
33. Kowaltowski AJ, Fenton RG, Fiskum G, (2004) Bcl-2 family proteins regulate mitochondrial reactive oxygen production and protect against oxidative stress. Free Radic Biol Med 37: 1845-1853.
34. Krishna S, Low IC, Pervaiz S, (2011) Regulation of mitochondrial metabolism: yet another facet in the biology of the oncoprotein Bcl-2. Biochem J 435: 545-551.
35. Jung MS, Jin DH, Chae HD, Kang S, Kim SC, et al. (2004) Bcl-xL and E1B-19K proteins inhibit p53-induced irreversible growth arrest and senescence by preventing reactive oxygen species-dependent p38 activation. J Biol Chem 279: 17765-17771.
36. Pathi SS, Lei P, Sreevalsan S, Chadalapaka G, Jutooru I, et al. (2011) Pharmacologic doses of ascorbic acid repress specificity protein (Sp) transcription factors and Sp-regulated genes in colon cancer cells. Nutr Cancer 63: 1133-1142.
37. Stadtman ER (1991) Ascorbic acid and oxidative inactivation of proteins. Am J Clin Nutr 54(6 Suppl): 1125S-1128S.
38. Du J, Cullen JJ, Buettner GR, (2012) Ascorbic acid: Chemistry, biology and the treatment of cancer. Biochim Biophys Acta 1826: 443-457.
39. Nemoto S, Otsuka M, Arakawa N, (1996) Inhibitory effect of ascorbate on cell growth: relation to catalase activity. J Nutr Sci Vitaminol (Tokyo) 42: 77-85.
40. Padayatty SJ, Sun AY, Chen Q, Espey MG, Drisko J, et al. (2010) Vitamin C: intravenous use by complementary and alternative medicine practitioners and adverse effects. PLoS One 5: e11414.
41. Hoffer LJ, Levine M, Assouline S, Melnychuk D, Padayatty SJ, et al. (2008) Phase I clinical trial of i.v. ascorbic acid in advanced malignancy. Ann Oncol 19: 1969-1974.
42. Padayatty SJ, Sun H, Wang Y, Riordan HD, Hewitt SM, et al. (2004) Vitamin C pharmacokinetics: implications for oral and intravenous use. Ann Intern Med 140: 533-537.
43. Semenza GL, (2003) Targeting HIF-1 for cancer therapy. Nat Rev Cancer 3: 721-732.
44. Aguayo A, Estey E, Kantarjian H, Mansouri T, Gidel C, et al. (1999) Cellular vascular endothelial growth factor is a predictor of outcome in patients with acute myeloid leukemia. Blood 94: 3717-3721.
45. Verstovsek S, Kantarjian H, Manshouri T, Cortes J, Giles FJ, et al. (2002) Prognostic significance of cellular vascular endothelial growth factor expression in chronic phase chronic myeloid leukemia. Blood 99: 2265-2267.
46. Knowles HJ, Raval RR, Harris AL, Ratcliffe PJ, (2003) Effect of ascorbate on the activity of hypoxia-inducible factor in cancer cells. Cancer Res 63: 1764-1768.
47. Packham G, (2008) The role of NF-kappaB in lymphoid malignancies. Br J Haematol 143: 3-15.
48. Braun T, Carvalho G, Fabre C, Grosjean J, Fenaux P, et al. (2006) Targeting NF-kappaB in hematologic malignancies. Cell Death Differ 13: 748-758.
49. Reikvam H, Olsnes AM, Gjertsen BT, Ersvar E, Bruserud Ø, (2009) Nuclear factor-kappaB signaling: a contributor in leukemogenesis and a target for pharmacological intervention in human acute myelogenous leukemia. Crit Rev Oncog 15: 1-41.
50. Liebes L, Krigel R, Kuo S, Nevrla D, Pelle E, et al. (1981) Increased ascorbic acid content in chronic lymphocytic leukemia B lymphocytes. Proc Natl Acad Sci USA 78: 6481-6484.
51. Vera JC, Rivas CI, Zhang RH, Farber CM, Golde DW, (1994) Human HL-60 myeloid leukemia cells transport dehydroascorbic acid via the glucose transporters and accumulate reduced ascorbic acid. Blood 84: 1628-1634.
52. Wang Y, Mackenzie B, Tsukaguchi H, Weremowicz S, Morton CC, et al. (2000) Human vitamin C (L-ascorbic acid) transporter SVCT1. Biochem Biophys Res Commun 267: 488-494.
53. Glaser SP, Lee EF, Trounson E, Bouillet P, Wei A, et al. (2012) Anti-apoptotic Mcl-1 is essential for the development and sustained growth of acute myeloid leukemia. Genes Dev 26: 120-125.
54. Del Principe MI, Del Poeta G, Venditti A, Buccisano F, Maurillo L, et al. (2005) Apoptosis and immaturity in acute myeloid leukemia. Hematology 10: 25-34.
55. Broome HE, Yu AL, Diccianni M, Camitta BM, Monia BP, et al. (2002) Inhibition of Bcl-xL expression sensitizes T-cell acute lymphoblastic leukemia cells to chemotherapeutic drugs. Leuk Res 26: 311-316.
56. Gonzalez MS, De Brasi CD, Bianchini M, Gargallo P, Moiraghi B, et al. (2010) BAX/BCL-XL gene expression ratio inversely correlates with disease progression in chronic myeloid leukemia. Blood Cells Mol Dis 45: 192-196.
57. Del Principe MI, Del Poeta G, Maurillo L, Buccisano F, Venditti A, et al. (2003) P-glycoprotein and BCL-2 levels predict outcome in adult acute lymphoblastic leukaemia. Br J Haematol 121: 730-738.
58. Pathi SS, Lei P, Sreevalsan S, Chadalapaka G, Jutooru I, et al. (2011) Pharmacologic doses of ascorbic acid repress specificity protein (Sp) transcription factors and Sp-regulated genes in colon cancer cells. Nutr Cancer 63: 1133-1142.
59. Jutooru I, Chadalapaka G, Sreevalsan S, Lei P, Barhoumi R, et al. (2010) Arsenic trioxide downregulates specificity protein (Sp) transcription factors and inhibits bladder cancer cell and tumor growth. Exp Cell Res 316: 2174-2188.
60. Jutooru I, Chadalapaka G, Lei P, Safe S, (2010) Inhibition of NFκB and pancreatic cancer cell and tumor growth by curcumin is dependent on specificity protein down-regulation. J Biol Chem 285: 25332-25344.
61. Jutooru I, Chadalapaka G, Abdelrahim M, Basha MR, Samudio I, et al. (2010) Methyl 2-cyano-3,12-dioxooleana-1,9-dien-28-oate decreases specificity protein transcription factors and inhibits pancreatic tumor growth: role of microRNA-27a. Mol Pharmacol 78: 226-236.
62. Sestili P, Brandi G, Brambilla L, Cattabeni F, Cantoni O, (1996) 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 277: 1719-1725.
63. Espey MG, Chen P, Chalmers B, Drisko J, Sun AY, et al. (2011) Pharmacologic ascorbate synergizes with gemcitabine in preclinical models of pancreatic cancer. Free Radic Biol Med 50: 1610-1619.