NO to cancer: The complex and multifaceted role of nitric oxide and the epigenetic nitric oxide donor, RRx-001

Redox Biology

Volumn 6, Issue , 2015, Pages 1-8

  Scicinski, Jan ^a   Oronsky, Bryan ^a   Ning, Shoucheng ^b   Knox, Susan ^b   Peehl, Donna ^c   Kim, Michelle M ^d   Langecker, Peter ^e   Fanger, Gary ^a  

^a EpicentRx   (United States)

^b STANFORD UNIVERSITY SCHOOL OF MEDICINE   (United States)

^c STANFORD UNIVERSITY   (United States)

^d UNIVERSITY OF MICHIGAN   (United States)

^e Women's Cancer Center   (United States)

Author keywords

Cancer; Hypoxia; Nitric oxide; Radiosensitization; Radiotherapy

Indexed keywords

NITRIC OXIDE; NITRIC OXIDE DONOR; NITRIC OXIDE DONOR RRX 001; OXYGEN; PEROXYNITRITE; RADIOSENSITIZING AGENT; REACTIVE NITROGEN SPECIES; REACTIVE OXYGEN METABOLITE; UNCLASSIFIED DRUG; ANTINEOPLASTIC AGENT; AZETIDINE DERIVATIVE; DEOXYHEMOGLOBIN; HEMOGLOBIN; INDUCIBLE NITRIC OXIDE SYNTHASE; NITRO DERIVATIVE; PROTEIN BINDING; RRX-001;

ABDOMINAL TUMOR; ARTICLE; BREAST TUMOR; CANCER RADIOTHERAPY; CELL RESPIRATION; CYTOTOXICITY; FEMALE GENITAL TRACT CANCER; FIBROSIS; HEAD AND NECK TUMOR; HUMAN; HYPOTENSION; HYPOXIA; MALIGNANT NEOPLASTIC DISEASE; NONHUMAN; OXYGENATION; PELVIS TUMOR; PRIORITY JOURNAL; PROSTATE CANCER; RADIATION DOSE; RADIOSENSITIZATION; STOMACH OBSTRUCTION; STOMACH PERFORATION; TUMOR BLOOD FLOW; TUMOR MICROENVIRONMENT; VASODILATATION; ANIMAL; CHEMISTRY; GAMMA RADIATION; GENETIC EPIGENESIS; GENETICS; METABOLISM; MOLECULAR MODEL; MOUSE; NEOPLASMS; OXIDATION REDUCTION REACTION; PATHOLOGY; THERAPEUTIC USE; VASCULARIZATION;

ANIMALS; ANTINEOPLASTIC AGENTS; AZETIDINES; EPIGENESIS, GENETIC; GAMMA RAYS; HEMOGLOBINS; HUMANS; HYPOXIA; MICE; MODELS, MOLECULAR; NEOPLASMS; NITRIC OXIDE; NITRIC OXIDE DONORS; NITRIC OXIDE SYNTHASE TYPE II; NITRO COMPOUNDS; OXIDATION-REDUCTION; OXYGEN; PROTEIN BINDING; RADIATION-SENSITIZING AGENTS;

EID: 84936871538     PISSN: 22132317     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.redox.2015.07.002     Document Type: Article

References (73)

1. Sarti P., Avigliano L., Gorlach A., Brune B. Superoxide and nitric oxide - participation in cell communication. Cell Death Differ. 2002, 9:1160-1162.
2. Gow A.J. The biological chemistry of nitric oxide as it pertains to the extrapulmonary effects of inhaled nitric oxide. Proc. Am. Thorac. Soc. 2006, 3:150-152.
3. Feelisch M., Martin J.F. The early role of nitric oxide in evolution. Trends Ecol. Evol. 1995, 10:496-499.
4. Yun H.Y., Dawson V.L., Dawson T.M. Nitric oxide in health and disease of the nervous system. Mol. Psychiatry 1997, 2:300-310.
5. Gladwin M.T., Schechter A.N. NO contest: nitrite versus S-nitroso-hemoglobin. Circ. Res. 2004, 94:851-855.
6. Hirst D.G., Robson T. Nitrosative stress in cancer therapy. Front. Biosci. 2007, 12:3406-3418.
7. Hirst D.G., Robson T. Nitrosative stress as a mediator of apoptosis: implications for cancer therapy. Curr. Pharm. Des. 2010, 16:45-55.
8. Harada H. How can we overcome tumor hypoxia in radiation therapy?. J. Radiat. Res. 2011, 52:545-556.
9. Harrison L., Blackwell K. Hypoxia and anemia: factors in decreased sensitivity to radiation therapy and chemotherapy?. Oncologist 2004, 9(Suppl. 5):S31-S40.
10. Oronsky B.T., Knox S.J., Scicinski J. Six degrees of separation: the oxygen effect in the development of radiosensitizers. Transl. Oncol. 2011, 4:189-198.
11. Oronsky B.T., Knox S.J., Scicinski J.J. Is nitric oxide (NO) the last word in radiosensitization? A review. Transl. Oncol. 2012, 5:66-71.
12. Beckman J.S., Koppenol W.H. Nitric oxide, superoxide, and peroxynitrite: the good, the bad, and ugly. Am. J. Physiol. 1996, 271:C1424-C1437.
13. Wang J., Torbenson M., Wang Q., Ro J.Y., Becich M. Expression of inducible nitric oxide synthase in paired neoplastic and non-neoplastic primary prostate cell cultures and prostatectomy specimen. Urol. Oncol. 2003, 21:117-122.
14. Jadeski L.C., Hum K.O., Chakraborty C., Lala P.K. Nitric oxide promotes murine mammary tumour growth and metastasis by stimulating tumour cell migration, invasiveness and angiogenesis. Int. J. Cancer 2000, 86:30-39.
15. Ng Q.S., Goh V., Milner J., Stratford M.R., Folkes L.K., Tozer G.M., Saunders M.I., Hoskin P.J. Effect of nitric-oxide synthesis on tumour blood volume and vascular activity: a phase I study. Lancet Oncol. 2007, 8:111-118.
16. Worthington J., Robson T., O'Keeffe M., Hirst D.G. Tumour cell radiosensitization using constitutive (CMV) and radiation inducible (WAF1) promoters to drive the iNOS gene: a novel suicide gene therapy. Gene Ther. 2002, 9:263-269.
17. Ning S., Bednarski M., Oronsky B., Scicinski J., Knox S.J. Novel nitric oxide generating compound glycidyl nitrate enhances the therapeutic efficacy of chemotherapy and radiotherapy. Biochem. Biophys. Res. Commun. 2014, 447:537-542.
18. Oronsky B., Fanger G.R., Oronsky N., Knox S., Scicinski J. The implications of hyponitroxia in cancer. Transl. Oncol. 2014, 7:167-173.
19. Wang C., Trudel L.J., Wogan G.N., Deen W.M. Thresholds of nitric oxide-mediated toxicity in human lymphoblastoid cells. Chem. Res. Toxicol. 2003, 16:1004-1013.
20. Heaton J.P., Adams M.A., Graham C.H., Emerson L., Siemens R.D. Evidence for the use of low dose nitric oxide in the treatment of rising PSA associated with biochemical failure following radical prostatectomy. J. Urol. 2003, 169(Suppl.):S1082.
21. De Ridder M., Van Esch G., Engels B., Verovski V., Storme G. Hypoxic tumor cell radiosensitization: role of the iNOS/NO pathway. Bull. Cancer 2008, 95:282-291.
22. De Ridder M., Verellen D., Verovski V., Storme G. Hypoxic tumor cell radiosensitization through nitric oxide. Nitric Oxide 2008, 19:164-169.
23. Folkes L.K., O'Neill P. DNA damage induced by nitric oxide during ionizing radiation is enhanced at replication. Nitric Oxide 2013, 34:47-55.
24. Folkes L.K., O'Neill P. Modification of DNA damage mechanisms by nitric oxide during ionizing radiation. Free Radic. Biol. Med. 2013, 58:14-25.
25. Cook T., Wang Z., Alber S., Liu K., Watkins S.C., Vodovotz Y., Billiar T.R., Blumberg D. Nitric oxide and ionizing radiation synergistically promote apoptosis and growth inhibition of cancer by activating p53. Cancer Res. 2004, 64:8015-8021.
26. Jordan B.F., Sonveaux P., Feron O., Gregoire V., Beghein N., Dessy C., Gallez B. Nitric oxide as a radiosensitizer: evidence for an intrinsic role in addition to its effect on oxygen delivery and consumption. Int. J. Cancer 2004, 109:768-773.
27. Wang X., Zalcenstein A., Oren M. Nitric oxide promotes p53 nuclear retention and sensitizes neuroblastoma cells to apoptosis by ionizing radiation. Cell Death Differ. 2003, 10:468-476.
28. Ducrocq C., Blanchard B., Pignatelli B., Ohshima H. Peroxynitrite: an endogenous oxidizing and nitrating agent. Cell. Mol. Life Sci. 1999, 55:1068-1077.
29. Szabo C., Ischiropoulos H., Radi R. Peroxynitrite: biochemistry, pathophysiology and development of therapeutics. Nat. Rev. Drug Discov. 2007, 6:662-680.
30. Brown G.C. Nitric oxide and mitochondria. Front. Biosci. 2007, 12:1024-1033.
31. Jordan B.F., Misson P., Demeure R., Baudelet C., Beghein N., Gallez B. Changes in tumor oxygenation/perfusion induced by the no donor, isosorbide dinitrate, in comparison with carbogen: monitoring by EPR and MRI. Int. J. Radiat. Oncol. Biol. Phys. 2000, 48:565-570.
32. Arrieta O., Blake M., de la Mata-Moya M.D., Corona F., Turcott J., Orta D., Alexander-Alatorre J., Gallardo-Rincon D. Phase II study. Concurrent chemotherapy and radiotherapy with nitroglycerin in locally advanced non-small cell lung cancer. Radiother. Oncol. 2014, 111:311-315.
33. Dhariwala F.A., Narang H., Krishna M. Differential response of three cell types to dual stress of nitric oxide and radiation. Cell Biol. Toxicol. 2012, 28:161-173.
34. Trotter M.J., Chaplin D.J., Olive P.L. Effect of angiotensin II on intermittent tumour blood flow and acute hypoxia in the murine SCCVII carcinoma. Eur. J. Cancer 1991, 27:887-893.
35. Bonaventura J. Clinical implications of the loss of vasoactive nitric oxide during red blood cell storage. Proc. Natl. Acad. Sci. U.S.A. 2007, 104:19165-19166.
36. Gladwin M.T., Ognibene F.P., Pannell L.K., Nichols J.S., Pease-Fye M.E., Shelhamer J.H., Schechter A.N. Relative role of heme nitrosylation and beta-cysteine 93 nitrosation in the transport and metabolism of nitric oxide by hemoglobin in the human circulation. Proc. Natl. Acad. Sci. U.S.A. 2000, 97:9943-9948.
37. Allen B.W., Piantadosi C.A. How do red blood cells cause hypoxic vasodilation? The SNO-hemoglobin paradigm. Am. J. Physiol. Heart Circ. Physiol. 2006, 291:H1507-H1512.
38. Sonveaux P., Lobysheva I.I., Feron O., McMahon T.J. Transport and peripheral bioactivities of nitrogen oxides carried by red blood cell hemoglobin: role in oxygen delivery. Physiology (Bethesda) 2007, 22:97-112.
39. 2 homeostasis. Curr. Opin. Genet. Dev. 1998, 8:588-594.
40. H. Jiang, M. De Ridder, V.N. Verovski, P. Sonveaux, B.F. Jordan, K. Law, C. Monsaert, D.L. Van den Berge, D. Verellen, O. Feron, et al., Activated macrophages as a novel determinant of tumor cell radioresponse: the role of nitric oxide-mediated inhibition of cellular respiration and oxygen sparing, Int. J. Radiat. Oncol. Biol. Phys. 76 (2010) 1520-1527.
41. Sonveaux P., Jordan B.F., Gallez B., Feron O. Nitric oxide delivery to cancer: why and how?. Eur. J. Cancer 2009, 45:1352-1369.
42. Hagen T., Taylor C.T., Lam F., Moncada S. Redistribution of intracellular oxygen in hypoxia by nitric oxide: effect on HIF1alpha. Science 2003, 302:1975-1978.
43. Stewart G.D., Nanda J., Katz E., Bowman K.J., Christie J.G., Brown D.J., McLaren D.B., Riddick A.C., Ross J.A., Jones G.D., et al. DNA strand breaks and hypoxia response inhibition mediate the radiosensitisation effect of nitric oxide donors on prostate cancer under varying oxygen conditions. Biochem. Pharmacol. 2011, 81:203-210.
44. Liebmann J., DeLuca A.M., Coffin D., Keefer L.K., Venzon D., Wink D.A., Mitchell J.B. In vivo radiation protection by nitric oxide modulation. Cancer Res. 1994, 54:3365-3368.
45. Maxhimer J.B., Soto-Pantoja D.R., Ridnour L.A., Shih H.B., Degraff W.G., Tsokos M., Wink D.A., Isenberg J.S., Roberts D.D. Radioprotection in normal tissue and delayed tumor growth by blockade of CD47 signaling. Sci. Transl. Med. 2009, 1:3ra7.
46. Soto-Pantoja D.R., Ridnour L.A., Wink D.A., Roberts D.D. Blockade of CD47 increases survival of mice exposed to lethal total body irradiation. Sci. Rep. 2013, 3:1038.
47. Soto-Pantoja D.R., Miller T.W., Pendrak M.L., DeGraff W.G., Sullivan C., Ridnour L.A., Abu-Asab M., Wink D.A., Tsokos M., Roberts D.D. CD47 deficiency confers cell and tissue radioprotection by activation of autophagy. Autophagy 2012, 8:1628-1642.
48. Rubbo H., Radi R., Trujillo M., Telleri R., Kalyanaraman B., Barnes S., Kirk M., Freeman B.A. Nitric oxide regulation of superoxide and peroxynitrite-dependent lipid peroxidation. Formation of novel nitrogen-containing oxidized lipid derivatives. J. Biol. Chem. 1994, 269:26066-26075.
49. Nguyen T., Nioi P., Pickett C.B. The Nrf2-antioxidant response element signaling pathway and its activation by oxidative stress. J. Biol. Chem. 2009, 284:13291-13295.
50. Howard-Flanders P. Effect of nitric oxide on the radiosensitivity of bacteria. Nature 1957, 180:1191-1192.
51. Wardman P., Rothkamm K., Folkes L.K., Woodcock M., Johnston P.J. Radiosensitization by nitric oxide at low radiation doses. Radiat. Res. 2007, 167:475-484.
52. Mitchell J.B., Wink D.A., DeGraff W., Gamson J., Keefer L.K., Krishna M.C. Hypoxic mammalian cell radiosensitization by nitric oxide. Cancer Res. 1993, 53:5845-5848.
53. Mitchell J.B., DeGraff W., Kim S., Cook J.A., Gamson J., Christodoulou D., Feelisch M., Wink D.A. Redox generation of nitric oxide to radiosensitize hypoxic cells. Int. J. Radiat. Oncol. Biol. Phys. 1998, 42:795-798.
54. Gao X., Saha D., Kapur P., Anthony T., Livingston E.H., Huerta S. Radiosensitization of HT-29 cells and xenografts by the nitric oxide donor DETANONOate. J. Surg. Oncol. 2009, 100:149-158.
55. Jordan B.F., Beghein N., Aubry M., Gregoire V., Gallez B. Potentiation of radiation-induced regrowth delay by isosorbide dinitrate in FSaII murine tumors. Int. J. Cancer 2003, 103:138-141.
56. Thews O., Kelleher D.K., Vaupel P. No improvement in perfusion and oxygenation of experimental tumors upon application of vasodilator drugs. Int. J. Oncol. 2001, 19:1243-1247.
57. Shan S.Q., Rosner G.L., Braun R.D., Hahn J., Pearce C., Dewhirst M.W. Effects of diethylamine/nitric oxide on blood perfusion and oxygenation in the R3230Ac mammary carcinoma. Br. J. Cancer 1997, 76:429-437.
58. Turek M., Padilla M., Argyle D.J. Evaluation of the gene for inducible nitric oxide synthase as a radiosensitizer under hypoxic and oxic conditions. Vet. Comp. Oncol. 2007, 5:250-255.
59. Robson T., Worthington J., McKeown S.R., Hirst D.G. Radiogenic therapy: novel approaches for enhancing tumor radiosensitivity. Technol. Cancer Res. Treat. 2005, 4:343-361.
60. Coulter J.A., McCarthy H.O., Worthington J., Robson T., Scott S., Hirst D.G. The radiation-inducible pE9 promoter driving inducible nitric oxide synthase radiosensitizes hypoxic tumour cells to radiation. Gene Ther. 2008, 15:495-503.
61. Reid T., Oronsky B., Infante J., Burris H., Scribner C., Knox S., Stephens J., Fanger G., Scicinski J. A phase 1 trial and pharmacokinetic study of RRx-001, a novel ROS-mediated pan-epigenetic agent. J. Clin. Oncol. 2014, Suppl.:S32. (abstr 2578).
62. Vitturi D.A., Sun C.W., Harper V.M., Thrash-Williams B., Cantu-Medellin N., Chacko B.K., Peng N., Dai Y., Wyss J.M., Townes T., et al. Antioxidant functions for the hemoglobin beta93 cysteine residue in erythrocytes and in the vascular compartment in vivo. Free Radic. Biol. Med. 2013, 55:119-129.
63. Scicinski J., Oronsky B., Cooper V., Taylor M., Alexander M., Hadar R., Cosford R., Fleischmann T., Fitch W.L. Development of methods for the bioanalysis of RRx-001 and metabolites. Bioanalysis 2014, 6:947-956.
64. Scicinski J., Oronsky B., Taylor M., Luo G., Musick T., Marini J., Adams C.M., Fitch W.L. Preclinical evaluation of the metabolism and disposition of RRx-001, a novel investigative anticancer agent. Drug Metab. Dispos. 2012, 40:1810-1816.
65. S. Ning, T. Sekar, R. Paulmurugan, J. Scicinski, B. Oronsky, D. Peehl, S. Knox, Molecular imaging of RRx-001-induced oxidative stress in Nrf2-luciferase expressing SCC VII tumors in mice, in: Proceedings of the AACR 105th Annual Meeting, San Diego, CA, 2014, pp. Abstr 906.
66. M.H.A.M. Fens, S.K. Larkin, C.R. Morris, B. Fitch, J. Scicinski, B. Oronsky, F.A. Kuypers, NO or no NO, increased reduction of nitrite to nitric oxide by modified red blood cells, in: ASH Annual Meeting Abstracts, vol. 118, 2011, p. 2125.
67. Fens M.H., Larkin S.K., Oronsky B., Scicinski J., Morris C.R., Kuypers F.A. The capacity of red blood cells to reduce nitrite determines nitric oxide generation under hypoxic conditions. PLoS One 2014, 9:e101626.
68. Grubina R., Huang Z., Shiva S., Joshi M.S., Azarov I., Basu S., Ringwood L.A., Jiang A., Hogg N., Kim-Shapiro D.B., et al. Concerted nitric oxide formation and release from the simultaneous reactions of nitrite with deoxy- and oxyhemoglobin. J. Biol. Chem. 2007, 282:12916-12927.
69. Cosby K., Partovi K.S., Crawford J.H., Patel R.P., Reiter C.D., Martyr S., Yang B.K., Waclawiw M.A., Zalos G., Xu X., et al. Nitrite reduction to nitric oxide by deoxyhemoglobin vasodilates the human circulation. Nat. Med. 2003, 9:1498-1505.
70. Ning S., Bednarski M., Oronsky B., Scicinski J., Saul G., Knox S.J. Dinitroazetidines are a novel class of anticancer agents and hypoxia-activated radiation sensitizers developed from highly energetic materials. Cancer Res. 2012, 72:2600-2608.
71. S. Ning, M. Bednarski, B. Oronsky, J. Scicinski, G. Saul, S. Knox, Dinitroazetidines are a novel class of anticancer agents and hypoxia-activated radiation sensitizers developed from highly energetic materials, in: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research, Orlando, Florida, 2011, pp. Abstract 676.
72. Kim S., Shen S., Moore D.F., Shih W., Lin Y., Li H., Dolan M., Shao Y.H., Lu-Yao G.L. Late gastrointestinal toxicities following radiation therapy for prostate cancer. Eur. Urol. 2011, 60:908-916.
73. Ning S., Tian J., Marshall D.J., Knox S.J. Anti-alphav integrin monoclonal antibody intetumumab enhances the efficacy of radiation therapy and reduces metastasis of human cancer xenografts in nude rats. Cancer Res. 2010, 70:7591-7599.