Ribonucleases with Antiproliferative Properties: Molecular Biological and Biochemical Characteristics

EXPERIMENTAL RESEARCH , , , , ,

VS Pokrovskii1, EM Treshchalina1, NV Andronova1, SM Deev2

1 N.N. Blokhin Russian Cancer Research Center, 24 Kashirskoye sh., Moscow, Russian Federation, 115478

2 M.M. Shemyakin and Yu.A. Ovchinnikov Institute of Bioorganic Chemistry, 16/10 Miklukho-Maklaya str., Moscow, Russian Federation, 117997

For correspondence: Vadim Sergeevich Pokrovskii, PhD, 24 Kashirskoye sh., Moscow, Russian Federation, 115478; Tel.: +7(499)324-14-09; e-mail: vadimpokrovsky@yandex.ru

For citation: Pokrovskii VS, Treshchalina EM, Andronova NV, Deev SM. Ribonucleases with Antiproliferative Properties: Molecular Biological and Biochemical Characteristics. Clinical oncohematology. 2016;9(2):130–7 (In Russ).

DOI: 10.21320/2500-2139-2016-9-2-130-137

ABSTRACT

The article dwells on ribonucleases (RNAses) whose cytotoxic activity depends on the enzymatic activity, i.e. the ability to catalyze the cleavage of phosphodiester bonds of RNA. It presents both well-known information and our own data on RNAses of different origins with antitumor properties; it investigates the relation between the mechanism of cytotoxicity and biochemical and molecular biological characteristics. The analysis of published data demonstrates that all above characteristics contribute to the antiproliferative activity of RNAses. The major challenge for this group of enzymes is the achieving of selective bioavailability. This problem can be solved by creating conjugates as in case with ranpirnase and barnase. Based on their major pharmacological properties, active antitumor RNAses have great perspectives for treatment of not only oncohematological, but also solid malignancies.

Keywords: ribonucleases, ranpirnase, amphinase, binase, barnase, pharmacological properties.

Received: January 4, 2016

Accepted: January 7, 2016

Read in PDF (RUS)pdficon

REFERENCES

  1. Deutscher MP, Li Z. Exoribonucleases and their multiple roles in RNA metabolism. Prog Nucl Acid Res Mol Biol. 2001;66:67–105. doi: 10.1016/s0079-6603(00)66027-0.
  2. Зеленихин П.В., Мамедзаде К.Р., Ильинская О.Н. Цитофлуориметрическая характеристика влияния РНКаз на клетки про- и эукариот. Гены и клетки. 2012;3(7):62–5.
    [Zelenikhin PV, Mamedzade KR, Ilinskaya ON. The cytofluorimetric characteristics of RNAse influence towards pro- and eucariotic cells. Geny i kletki. 2012;3(7):62–5. (In Russ)]
  3. Ledoux L. Action of ribonuclease on two solid tumours in vivo. Nature. 1955;176(4470):36–7. doi: 10.1038/176036a0.
  4. Edelweiss E, Balandin TG, Ivanova JL, et al. Barnase as a new therapeutic agent triggering apoptosis in human cancer cells. PLoS ONE. 2008;3(6):e2434. doi: 10.1371/journal.pone.0002434.
  5. Глинка Е.М., Эдельвейс Э.Ф., Деев С.М. Эукариотические экспрессирующие векторы и иммуноконъюгаты для терапии рака. Биохимия. 2006;71:597–60.
    [Glinka EM, Edel’veis EF, Deev SM. Eukaryotic expressing vectors and immunoconjugates for treatment of cancer. Biokhimiya. 2006;71:597–60. (In Russ)]
  6. Deyev SM, Lebedenko EN, Petrovskaya LE, et al. Man-made antibodies and immunoconjugates with desired properties: function optimization using structure engineering. Russ Chem Rev. 2015;84(1):1–26. doi: 10.1070/RCR4459.
  7. Mitkevich VA, Tchurikov NA, Zelenikhin PV, et al. Binase cleaves cellular noncoding RNAs and affects coding mRNAs. FEBS J. 2010;277(1):186–96. doi: 10.1111/j.1742-4658.2009.07471.x.
  8. Кабрера Фуентес Э.А., Зеленихин П.В., Колпаков А.И. и др. Сравнительная цитотоксичность биназы по отношению к опухолевым и нормальным клеткам. Ученые записки Казанского университета. Серия: Естественные науки. 2010;152(3):143–8.
    [Caberra Fuentes HA, Zelenikhin PV, Kolpakov AI, et al. Comparative Toxicity of Binase towards Tumor and Normal Cells. Uchenye zapiski Kazanskogo universiteta. Seriya: Estestvennye nauki. 2010;152(3):143–8. (In Russ)]
  9. Darzynkiewicz Z, Carter SP, Mikulski SM, et al. Cytostatic and cytotoxic effects of Pannon (P-30 Protein), a novel anticancer agent. Cell Tissue Kinet. 1988;21(3):169–82. doi: 10.1111/j.1365-2184.1988.tb00855.x.
  10. Ardelt W, Mikulski SM, Shogen K. Amino acid sequence of an anti-tumor protein from Rana pipiens oocytes and early embryos. Homology to pancreatic ribonucleases. Biol Chem. 1991;266(1):245–51.
  11. Raines RT. Active site of ribonuclease A. In: Zenkova MA, ed. Artificial Nucleases. Heidelberg: Springer Verlag; 2004. pp. 19–32.
  12. Juan G, Ardelt B, Mikulski SM, et al. G1 arrest of U-937 cells by onconase is associated with suppression of cyclin D3 expression, induction of p16INK4A, p21WAF1/CIP1 and p27KIP and decreased pRb phosphorylation. Leukemia. 1998;12(8):1241–8. doi: 10.1038/sj.leu.2401100.
  13. Deptala A, Halicka HD, Ardelt B, et al. Potentiation of tumor necrosis factor induced apoptosis by onconase. Int J Oncol. 1998;13(1):11–6. doi: 10.3892/ijo.13.1.11.
  14. Tsai SY, Ardelt B, Hsieh TC, et al. Treatment of Jurkat acute T-lymphocytic leukemia cells by onconase (Ranpirnase) is accompanied by an altered nucleocytoplasmic distribution and reduced expression of transcription factor NF-kappaB. Int J Oncol. 2004;25(6):1745–52. doi: 10.3892/ijo.25.6.1745.
  15. Rodriguez M, Torrent G, Bosch M, et al. Intracellular pathway of Onconase that enables its delivery to the cytosol. J Cell Sci. 2007;120(8):1405–11. doi: 10.1242/jcs.03427.
  16. Marquez M, Nilsson S, Lennartsson L, et al. Charge dependent targeting: Results in six tumor cell lines. Anticancer Res. 2004;24:1347–51.
  17. Leland PA, Raines RT. Cancer chemotherapy: ribonucleases to the rescue. Chem Biol. 2001;8(5):405–13. doi: 10.1016/s1074-5521(01)00030-8.
  18. Wu Y, Mikulski SM, Ardelt W, et al. A cytotoxic ribonuclease. Study of the mechanism of onconase cytotoxicity. J Biol Chem. 1993;268(14):10686–93.
  19. Saxena SK, Sirdeshmukh R, Ardelt W, et al. Entry into cells and selective degradation of tRNAs by a cytotoxic member of the RNase A family. J Biol Chem. 2002;277(17):15142–6. doi: 10.1074/jbc.m10811520020.
  20. Suhasini AN, Sirdeshmukh R. Transfer RNA cleavages by onconase reveal unusual cleavage sites. J Biol Chem. 2006;281(18):12201–9. doi: 10.1074/jbc.m504488200.
  21. Gong J, Li X, Darzynkiewicz Z. Different patterns of apoptosis of HL-60 cells induced by cycloheximide and camptothecin. J Cell Physiol. 1993;157(2):263–70. doi: 10.1002/jcp.1041570208.
  22. Ardelt B, Ardelt W, Darzynkiewicz Z. Cytotoxic ribonucleases and RNA interference (RNAi). Cell Cycle 2003;2(1):22–4. doi: 10.4161/cc.2.1.232.
  23. Zhao H, Ardelt B, Ardelt W, et al. The cytotoxic ribonuclease Onconase targets RNA interference (siRNA). Cell Cycle. 2008;7(20):3258–61. doi: 10.4161/cc.7.20.6855.
  24. Volinia S, Calin GA, Liu CG, et al. A microRNAs expression signature of human solid tumors defines cancer gene targets. Proc Natl Acad Sci USA. 2006;103(7):2257–61. doi: 10.1073/pnas.0510565103.
  25. Basseres DS, Baldwin AS. Nuclear factor-kappaB and inhibitor of kappaB kinase pathways in oncogenic initiation and progression. Oncogene. 2006;30(25):6817–30. doi: 10.1038/sj.onc.1209942.
  26. Lee I, Kalota A, Gewirtz AM, Shogen K. Antitumor efficacy of the cytotoxic RNase, ranpirnase, on A549 human lung cancer xenografts of nude mice. Anticancer Res. 2007;27(1A):299–307.
  27. Lee I, Lee YH, Mikulski SM, Shogen K. Effect of onconase +/- tamoxifen on ASPC-1 human pancreatic tumors in nude mice. Adv Exp Med Biol. 2003;530:187–96. doi: 10.1007/978-1-4615-0075-9_18
  28. Rybak SM, Pearson JW, Fogler WE, et al. Enhancement of vincristine cytotoxicity in drug-resistant cells by simultaneous treatment with onconase, an antitumor ribonuclease. J Natl Cancer Inst. 1996;88(11):747–53. doi: 10.1093/jnci/88.11.747.
  29. Ita M, Halicka HD, Tanaka T, et al. Remarkable enhancement of cytotoxicity of onconase and cepharanthine when used in combination on various tumor cell lines. Cancer Biol Ther. 2008;7(7):1104–8. doi: 10.4161/cbt.7.7.6172.
  30. Smolewski P, Witkowska M, Zwolinska M, et al. Cytotoxic activity of the amphibian ribonucleases onconase and r-amphinase on tumor cells from B cell lymphoproliferative disorders. Int J Oncol. 2014;45(1):419–25. doi: 10.3892/ijo.2014.2405.
  31. Majchrzak A, Witkowska M, Medra A, et al. In vitro cytotoxicity of ranpirnase (onconase) in combination with components of R-CHOP regimen against diffuse large B cell lymphoma (DLBCL) cell line. Postepy Hig Med Dosw. 2013;67:1166–72. doi: 10.5604/17322693.107838632.
  32. Porta C, Paglino C, Mutti L. Ranpirnase and its potential for the treatment of unresectable malignant mesothelioma. Biologics. 2008;2(4):601–9. doi: 10.2147/btt.s2383.
  33. Costanzi J, Sidransky D, Navon A, et al. Ribonucleases as a novel pro-apoptotic anticancer strategy: review of the preclinical and clinical data for ranpirnase. Cancer Invest. 2005;23(7):643–50. doi: 10.1080/07357900500283143.
  34. Mikulski SM, Costanzi JJ, Vogelzang NJ, et al. Phase II trial of a single weekly intravenous dose of ranpirnase in patients with unresectable malignant mesothelioma. J Clin Oncol. 2002;20(1):274–81. doi: 10.1200/jco.20.1.274.
  35. Vasandani VM, Burris JA, Sung C. Reversible nephrotoxicity of onconase and effect of lysine pH on renal onconase uptake. Cancer Chemother Pharmacol. 1999;44(2):164–9. doi: 10.1007/s002800050962.
  36. Singh UP, Ardelt W, Saxena SK, et al. Enzymatic and Structural Characterisation of Amphinase, a Novel Cytotoxic Ribonuclease from Rana pipiens Oocytes. J Mol Biol. 2007;371(1):93–111. doi: 10.1016/j.jmb.2007.04.071.
  37. Ardelt B, Ardelt W, Pozarowski P, et al. Cytostatic and cytotoxic properties of Amphinase: a novel cytotoxic ribonuclease from Rana pipiens oocytes. Cell Cycle. 2007;6(24):3097–102. doi: 10.4161/cc.6.24.5045.
  38. Sevcik J, Sanishili RG, Pavlovsky AG, Polyakov KM. Comparison of active sites of some microbial ribonucleases: structural basis for guanylic specificity. Trends Biochem Sci. 1990;15(4):158–62. doi: 10.1016/0968-0004(90)90217-y.
  39. Makarov AA, Ilinskaya ON. Cytotoxic ribonucleases: molecular weapons and their targets. FEBS Lett. 2003;540(1–3):15–20. doi: 10.1016/s0014-5793(03)00225-4.
  40. Makarov AA, Kolchinski A, Ilinskaya ON. Binase and other microbial RNases as potential anticancer agents. BioEssays. 2008;30(8):789–90. doi: 10.1002/bies.20789.
  41. Ильинская О.Н., Макаров А.А. Почему рибонуклеазы вызывают гибель раковых клеток. Молекулярная биология. 2005;39(1):3–13.
    [Il’inskaya ON, Makarov AA. Why ribonucleases cause tumor cell death. Molekulyarnaya biologiya. 2005;39(1):3–13. (In Russ)]
  42. Ильинская О.Н., Зеленихин П.В., Колпаков А.И. и др. Избирательная цитотоксичность биназы в отношении фибробластов, экспрессирующих онкогены ras и AML/ETO. Ученые записки Казанского университета. Серия: Естественные науки. 2008;150(4):268–73.
    [Ilinskaya ON, Zelenikhin PV, Kolpakov AI, et al. Selective Cytotoxicity of Binase towards Fibroblasts with Expression of the ras- and AML/ETO Oncogenes. Uchenye zapiski Kazanskogo universiteta. Seriya: Estestvennye nauki. 2008;150(4):268–73. (In Russ)]
  43. Mitkevich VA, Petrushanko IY, Spirin PV, et al. Sensitivity of acute myeloid leukemia Kasumi-1 cells to binase toxic action depends on the expression of KIT and АML1-ETO oncogenes. Cell Cycle. 2011;10(23):4090–7. doi: 10.4161/cc.10.23.18210.
  44. Mitkevich VA, Kretova OV, Petrushanko IY, et al. Ribonuclease binase apoptotic signature in leukemic Kasumi-1 cells. Biochimie. 2013;95(6):1344–9. doi: 10.1016/j.biochi.2013.02.016.
  45. Петрушанко И.Ю., Зеленихин П.В., Митькевич В.А. и др. Биназа обладает избирательным цитотоксическим действием на kit-трансформированные предшественники миелоидных клеток. Биофизика. 2007;52(5):876–81.
    [Petrushanko IYu, Zelenikhin PV, Mit’kevich VA, et al. Binasa produces selective cytotoxic effect on kit-transformed myeloid cell precursors. Biofizika. 2007;52(5):876–81. (In Russ)]
  46. Зеленихин П.В., Колпаков А.И., Черепнев Г.В., Ильинская О.Н. Индукция апоптоза опухолевых клеток биназой. Молекулярная биология. 2005;39(3):457–63.
    [Zelenikhin PV, Kolpakov AI, Cherepnev GV, Il’inskaya ON. Induction of tumor cell apoptosis by binasa. Molekulyarnaya biologiya. 2005;39(3):457–63. (In Russ)]
  47. Трещалина Е.М. Коллекция опухолевых штаммов человека. М.: Практическая медицина, 2009. 70 с.
    [Treshchalina EM. Kollektsiya opukholevykh shtammov cheloveka. (Collection of human tumor strains.) Moscow: Prakticheskaya Meditsina Publ.; 2009. 70 p. (In Russ)]
  48. Трещалина Е.М. Иммунодефицитные мыши разведения РОНЦ им. Н.Н. Блохина РАМН. Возможности использования. М.: Издательская группа РОНЦ, 2010. 16 с.
    [Treshchalina EM. Immunodefitsitnye myshi razvedeniya RONTs im. N.N. Blokhina RAMN. Vozmozhnosti ispol’zovaniya. (Mice with immune deficiency bred in NN Blokhin Russian Cancer Research Center. Opportunities for use.) Moscow: Izdatel’skaya gruppa RONTs Publ.; 2010. 16 p. (In Russ)]
  49. Трещалина Е.М., Жукова О.С., Герасимова Г.К. и др. Методические рекомендации по доклиническому изучению противоопухолевой активности лекарственных средств. В кн.: Руководство по проведению доклинических исследований лекарственных средств. Часть первая. М.: Гриф и К, 2012. С. 642–57.
    [Treshchalina EM, Zhukova OS, Gerasimova GK, et al. Guidelines for pre-clinical studies of antitumor activity of drugs. In: Rukovodstvo po provedeniyu doklinicheskikh issledovanii lekarstvennykh sredstv. (Guidelines for pre-clinical studies of medicinal agents.) Part 1. Moscow: Grif i K Publ.; 2012. pp. 642–57. (In Russ)]
  50. Ulyanova V, Vershinina V, Ilinskaya O. Barnase and binase: twins with distinct fates. FEBS J. 2011;8(19):3633–43. doi: 10.1111/j.1742-4658.2011.08294.x.
  51. Hoefling M, Gottschalk KE. Barnase–barstar: from first encounter to final complex. J Struct Biol. 2010;171(1):52–63. doi: 10.1016/j.jsb.2010.03.001.
  52. Deyev SM, Yazynin SA, Kuznetsov DA, et al. Ribonuclease-charged vector for facile direct cloning with positive selection. Mol Gen Genet. 1998;259(4):379–82. doi: 10.1007/s004380050825.
  53. Semenyuk EG, Stremovskiy OA, Edelweiss EF, et al. Expression of single-chain antibody–barstar fusion in plants. Biochimie. 2007;89(1):31–8. doi: 10.1016/j.biochi.2006.07.012.
  54. Liao YD, Huang HC, Chan HJ, Kuo SJ. Large-scale preparation of a ribonuclease from Rana catesbeiana (bullfrog) oocytes and characterization of its specific cytotoxic activity against tumor cells. Prot Express Purif. 1996;7(2):194–202. doi: 10.1006/prep.1996.0027.
  55. Tatsuta T, Sugawara S, Takahashi K, et al. Cancer-selective induction of apoptosis by leczyme. Front Oncol. 2014;4:139. doi: 10.3389/fonc.2014.00139.
  56. Zhang R, Zhao L, Wang H, Ng TB. A novel ribonuclease with antiproliferative activity toward leukemia and lymphoma cells and HIV-1 reverse transcriptase inhibitory activity from the mushroom, Hohenbuehelia serotina. Int J Mol Med. 2014;33(1):209–14.
  57. Tatsuta T, Sugawara S, Takahashi K, et al. Leczyme: A New Candidate Drug for Cancer Therapy. BioMed Re Intern. 2014. doi: 10.1155/2014/421415.
  58. Nitta K, Ozaki K, Ishikawa M, et al. Inhibition of cell proliferation by Rana catesbeiana and Rana japonica lectins belonging to the ribonuclease superfamily. Cancer Res. 1994;54(4):920–7.
  59. Tatsuta T, Hosono M, Sugawara S, et al. Sialic acid-binding lectin (leczyme) induces caspase-dependent apoptosis-mediated mitochondrial perturbation in Jurkat cells. Intern J Oncol. 2013;43(5):1402–12. doi: 10.3892/ijo.2013.2092.
  60. Glinka EM, Edelweiss EF, Sapozhnikov AM, Deyev SM. A new vector for controllable expression of an anti-HER2/neu mini-antibody-barnase fusion protein in HEK 293T cells. Gene. 2006;366(1):97–103. doi: 10.1016/j.gene.2005.06.042.
  61. Chang CH, Sapra P, Vanama SS, et al. Effective therapy of human lymphoma xenografts with a novel recombinant ribonuclease/anti-CD74 humanized IgG4 antibody immunotoxin. Blood. 2005;106(13):4308–14. doi: 10.1182/blood-2005-03-1033.
  62. Newton DL, Stockwin LH, Rybak SM. Anti-CD22 Onconase: preparation and characterization. Meth Mol Biol. 2009;525:425–43. doi: 10.1007/978-1-59745-554-1_22.
  63. Newton DL, Hansen HJ, Mikulski SM, et al. Potent and specific antitumor effects of an anti-CD22-targeted cytotoxic ribonuclease: potential for the treatment of non-Hodgkin lymphoma. Blood. 2001;97(2):528–35. doi: 10.1182/blood.v97.2.528.
  64. Глинка Е.M., Эдельвейс Э.Ф., Деев С.М. Эукариотические экспрессирующие векторы и иммуноконъюгаты для терапии рака. Биохимия. 2006;71(6):742–53.
    [Glinka EM, Edel’veis EF, Deev SM. Eukaryotic expressing vectors and immunoconjugates for treatment of cancer. Biokhimiya. 2006;71(6):742–53. (In Russ)]
  65. Deyev SM, Lebedenko EN. Modern technologies for creating synthetic antibodies for clinical application. Acta Naturae. 2009;1(1):32–50.
  66. Эдельвейс Э.Ф. Иммунобарназные конъюгаты для диагностики и терапии рака: Автореф. дис. ¼ канд. биол. наук. М., 2010. 24 с.
    [Edel’veis EF. Immunobarnaznye kon’yugaty dlya diagnostiki i terapii raka. (Immunobarnase conjugates for diagnosis and treatment of cancer.) [dissertation] Moscow; 2010. 24 p. (In Russ)]
  67. Эдельвейс Э.Ф., Баландин Т.Г., Стремовский О.А. и др. Иммуноконъюгат анти-EGFR-мини-антитело–барназа высокотоксичен для опухолевых клеток человека. Доклады Академии наук. 2010;434(4):558–61.
    [Edel’veis EF, Balandin TG, Stremovskii OA, et al. Anti-anti-EGFR–barnase immunoconjugate is highly toxic for human tumor cells. Doklady Akademii nauk. 2010;434(4):558–61. (In Russ)]
  68. Schirrmann T, Krauss J, Arndt MA, et al. Targeted therapeutic RNases (ImmunoRNases). Expert Opin Biol Ther. 2009;9:79–95. doi: 10.1517/14712590802631862.
  69. De Lorenzo C, Arciello A, Cozzolino R, et al. A fully human antitumor immunoRNase selective for ErbB-2-positive carcinomas. Cancer Res. 2004;64(14):4870–4. doi: 10.1158/0008-5472.can-03-3717.
  70. De Lorenzo C, Tedesco A, Terrazzano G, et al. A human, compact, fully functional anti-ErbB2 antibody as a novel antitumour agent. Br J Cancer. 2004;91(6):1200–4. doi: 10.1038/sj.bjc.6602110.
  71. Покровский В.С., Трещалина Е.М. Ферментные препараты в онкогематологии: актуальные направления экспериментальных исследований и перспективы клинического применения. Клиническая онкогематология. 2014;7(1):28–39.
    [Pokrovskii VS, Treshchalina EM. Enzymes in oncohaematology: relevant directions of experimental studies and prospects of clinical use. Klinicheskaya onkogematologiya. 2014;7(1):28–39. (In Russ)]
  72. Покровский В.С., Лесная Н.А., Трещалина Е.М. и др. Перспективы разработки новых ферментных противоопухолевых препаратов. Вопросы онкологии. 2011;57(2):155–64.
    [Pokrovskii VS, Lesnaya NA, Treshchalina EM, et al. Perspectives of development of novel enzymatic antitumor agents. Voprosy onkologii. 2011;57(2):155–64. (In Russ)]
  73. Hatlen MA, Wang L, Nimer SD. AML1-ETO driven acute leukemia: insights into pathogenesis and potential therapeutic approaches. Front Med. 2012;6(3):248–62. doi: 10.1007/s11684-012-0206-6.
  74. Ziai JM, Siddon AJ, et al. Pathology Consultation on Gene Mutations in Acute Myeloid Leukemia. Am J Clin Pathol. 2015;144(4):539–54. doi: 10.1309/AJCP77ZFPUQGYGWY.