Mechanisms of Antiproliferative Action of Streptococcal Arginine Deiminase Against Jurkat Lymphoblastic Leukemia Cells

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Abstract

Arginine deprivation strategy is considered as a promising trend in cancer therapy. The aim of the study was to investigate the influence of streptococcal arginine deiminase on Jurkat lymphoblastic leukemia cells. The effects of the supernatants of the destroyed streptococci of the original strain expressing arginine deiminase and its isogenic mutant with the inactivated arcA gene were compared. Cell proliferation was evaluated in an MTT-test. The remaining parameters were examined using flow cytometry. The cell cy-cle changes were studied using DAPI dye and anti-cyclin A2 antibodies. The autophagy intensity was assessed using the LysoTracker ™ Green DND-26 reagent. To investigate cell viability DAPI staining was performed. Streptococcal arginine deiminase suppressed proliferative activity Jurkat lymphoblastic leukemia cells, increased the proportion of cells in the G0/G1 phases, reduced S/G2 phases proportion of cells and enhanced autophagy, without declaing viability. Arginine supplementation leveled the effects of the enzyme. The obtained results open up the possibility of using arginine-hydrolyzing activity of the streptococcal enzyme for combined therapy of oncological diseases.

About the authors

E. A. Starikova

Institute of Experimental Medicine; The First St. Petersburg State Medical University named after academician I.P. Pavlov
of the Ministry of Health of the Russian Federation; Institute of Medical Education, Almazov National Medical Research Centre of the Ministry
of Health of the Russian Federation

Author for correspondence.
Email: Starickova@yandex.ru
Russia, Saint-Petersburg; Russia, Saint-Petersburg; Russia, Saint-Petersburg

J. T. Mammedova

Institute of Experimental Medicine

Email: Starickova@yandex.ru
Russia, Saint-Petersburg

A. Ozhiganova

Institute of Experimental Medicine

Email: Starickova@yandex.ru
Russia, Saint-Petersburg

L. A. Burova

Institute of Experimental Medicine

Email: Starickova@yandex.ru
Russia, Saint-Petersburg

I. V. Kudryavtsev

Institute of Experimental Medicine; The First St. Petersburg State Medical University named after academician I.P. Pavlov
of the Ministry of Health of the Russian Federation

Email: Starickova@yandex.ru
Russia, Saint-Petersburg; Russia, Saint-Petersburg

References

  1. Morris SM Jr (2016) Arginine Metabolism Revisited. J Nutrition 146: 2579S–2586S. https://doi.org/10.3945/jn.115.226621
  2. Kirk SJ, Barbul A (1990) Role of arginine in trauma, sepsis, and immunity. JPEN J Parenter Enteral Nutr 14: 226S–229S. https://doi.org/10.1177/014860719001400514
  3. Starikova EA, Rubinstein AA, Mammedova JT, Isakov DV, Kudryavtsev IV (2023) Regulated Arginine Metabolism in Immunopathogenesis of a Wide Range of Diseases: Is There a Way to Pass between Scylla and Charybdis? Current Issues Mol Biol 45: 3525–3551. https://doi.org/10.3390/cimb45040231
  4. Morris CR (2014) Alterations of the arginine metabolome in sickle cell disease: a growing rationale for arginine therapy. Hematol Oncol Clin North Am 28: 301–321. https://doi.org/10.1016/j.hoc.2013.11.008
  5. Morris CR, Kim H-Y, Klings ES, Wood J, Porter JB, Trachtenberg F, Sweeters N, Olivieri NF, Kwiatkowski JL, Virzi L, Hassell K, Taher A, Neufeld EJ, Thompson AA, Larkin S, Suh JH, Vichinsky EP, Kuypers FA, Thalassemia Clinical Research Network (2015) Dysregulated arginine metabolism and cardiopulmonary dysfunction in patients with thalassaemia. Br J Haematol 169: 887–898. https://doi.org/10.1111/bjh.13452
  6. Morris CR (2008) Mechanisms of vasculopathy in sickle cell disease and thalassemia. Hematology Am Soc Hematol Educ Program 177–185. https://doi.org/10.1182/asheducation-2008.1.177
  7. Morris CR, Kuypers FA, Lavrisha L, Ansari M, Sweeters N, Stewart M, Gildengorin G, Neumayr L, Vichinsky EP (2013) A randomized, placebo-controlled trial of arginine therapy for the treatment of children with sickle cell disease hospitalized with vaso-occlusive pain episodes. Haematologica 98: 1375–1382. https://doi.org/10.3324/haematol.2013.086637
  8. Morris CR, Poljakovic M, Lavrisha L, Machado L, Kuypers FA, Morris SM (2004) Decreased arginine bioavailability and increased serum arginase activity in asthma. Am J Respir Crit Care Med 170: 148–153. https://doi.org/10.1164/rccm.200309-1304OC
  9. Morris CR (2013) Arginine and asthma. Nestle Nutr Inst Workshop Ser 77: 1–15. https://doi.org/10.1159/000351365
  10. Hsu C-N, Tain Y-L (2019) Impact of Arginine Nutrition and Metabolism during Pregnancy on Offspring Outcomes. Nutrients 11: 1452. https://doi.org/10.3390/nu11071452
  11. Clark A, Imran J, Madni T, Wolf SE (2017) Nutrition and metabolism in burn patients. Burns & Trauma 5: 11. https://doi.org/10.1186/s41038-017-0076-x
  12. Pribis JP, Zhu X, Vodovotz Y, Ochoa JB (2012) Systemic Arginine Depletion After a Murine Model of Surgery or Trauma. JPEN J Parenter Enteral Nutr 36: 53–59. https://doi.org/10.1177/0148607111414579
  13. Bernard AC, Mistry SK, Morris SM, O’Brien WE, Tsuei BJ, Maley ME, Shirley LA, Kearney PA, Boulanger BR, Ochoa JB (2001) Alterations in arginine metabolic enzymes in trauma. Shock 15: 215–219. https://doi.org/10.1097/00024382-200115030-00009
  14. Martí I Líndez A-A, Reith W (2021) Arginine-dependent immune responses. Cell Mol Life Sci 78: 5303–5324. https://doi.org/10.1007/s00018-021-03828-4
  15. Albaugh VL, Pinzon-Guzman C, Barbul A (2017) Arginine-Dual roles as an onconutrient and immunonutrient. J Surg Oncol 115: 273–280. https://doi.org/10.1002/jso.24490
  16. Zhao C, Guo H, Hou Y, Lei T, Wei D, Zhao Y (2023) Multiple Roles of the Stress Sensor GCN2 in Immune Cells. Int J Mol Sci 24: 4285. https://doi.org/10.3390/ijms24054285
  17. Patil MD, Bhaumik J, Babykutty S, Banerjee UC, Fukumura D (2016) Arginine dependence of tumor cells: targeting a chink in cancer’s armor. Oncogene 35: 4957–4972. https://doi.org/10.1038/onc.2016.37
  18. Chen C-L, Hsu S-C, Ann DK, Yen Y, Kung H-J (2021) Arginine Signaling and Cancer Metabolism. Cancers (Basel) 13: 3541. https://doi.org/10.3390/cancers13143541
  19. Jung CH, Jun CB, Ro S-H, Kim Y-M, Otto NM, Cao J, Kundu M, Kim D-H (2009) ULK-Atg13-FIP200 complexes mediate mTOR signaling to the autophagy machinery. Mol Biol Cell 20: 1992–2003. https://doi.org/10.1091/mbc.e08-12-1249
  20. Szlosarek PW (2014) Arginine deprivation and autophagic cell death in cancer. Proc Natl Acad Sci U S A 111: 14015–14016. https://doi.org/10.1073/pnas.1416560111
  21. Ishimwe N, Zhang W, Qian J, Zhang Y, Wen L (2020) Autophagy regulation as a promising approach for improving cancer immunotherapy. Cancer Lett 475: 34–42. https://doi.org/10.1016/j.canlet.2020.01.034
  22. Hackett CS, Quigley DA, Wong RA, Chen J, Cheng C, Song YK, Wei JS, Pawlikowska L, Bao Y, Goldenberg DD, Nguyen K, Gustafson WC, Rallapalli SK, Cho Y-J, Cook JM, Kozlov S, Mao J-H, Van Dyke T, Kwok P-Y, Khan J, Balmain A, Fan Q, Weiss WA (2014) Expression quantitative trait loci and receptor pharmacology implicate Arg1 and the GABA-A receptor as therapeutic targets in neuroblastoma. Cell Rep 9: 1034–1046. https://doi.org/10.1016/j.celrep.2014.09.046
  23. Sousa MSA, Latini FRM, Monteiro HP, Cerutti JM (2010) Arginase 2 and nitric oxide synthase: Pathways associated with the pathogenesis of thyroid tumors. Free Radic Biol Med 49: 997–1007. https://doi.org/10.1016/j.freeradbiomed.2010.06.006
  24. Yu Y, Ladeiras D, Xiong Y, Boligan KF, Liang X, von Gunten S, Hunger RE, Ming X-F, Yang Z (2020) Arginase-II promotes melanoma migration and adhesion through enhancing hydrogen peroxide production and STAT3 signaling. J Cell Physiol 235: 9997–10011. https://doi.org/10.1002/jcp.29814
  25. Belgorosky D, Girouard J, Langle YV, Hamelin-Morrissete J, Marino L, Agüero EI, Malagrino H, Reyes-Moreno C, Eiján AM (2020) Relevance of iNOS expression in tumor growth and maintenance of cancer stem cells in a bladder cancer model. J Mol Med (Berl) 98: 1615–1627. https://doi.org/10.1007/s00109-020-01973-0
  26. Girotti AW, Fahey JM, Korytowski W (2020) Nitric oxide-elicited resistance to anti-glioblastoma photodynamic therapy. Cancer Drug Resist 3: 401–414. https://doi.org/10.20517/cdr.2020.25
  27. Gallego P, Planell R, Benach J, Querol E, Perez-Pons JA, Reverter D (2012) Structural characterization of the enzymes composing the arginine deiminase pathway in Mycoplasma penetrans. PLoS One 7: e47886. https://doi.org/10.1371/journal.pone.0047886
  28. Hirose Y, Yamaguchi M, Sumitomo T, Nakata M, Hanada T, Okuzaki D, Motooka D, Mori Y, Kawasaki H, Coady A, Uchiyama S, Hiraoka M, Zurich RH, Amagai M, Nizet V, Kawabata S (2021) Streptococcus pyogenes upregulates arginine catabolism to exert its pathogenesis on the skin surface. Cell Rep 34: 108924. https://doi.org/10.1016/j.celrep.2021.108924
  29. Zhang L, Liu M, Jamil S, Han R, Xu G, Ni Y (2015) PEGylation and pharmacological characterization of a potential anti-tumor drug, an engineered arginine deiminase originated from Pseudomonas plecoglossicida. Cancer Lett 357: 346–354. https://doi.org/10.1016/j.canlet.2014.11.042
  30. Abou-Alfa GK, Qin S, Ryoo B-Y, Lu S-N, Yen C-J, Feng Y-H, Lim HY, Izzo F, Colombo M, Sarker D, Bolondi L, Vaccaro G, Harris WP, Chen Z, Hubner RA, Meyer T, Sun W, Harding JJ, Hollywood EM, Ma J, Wan PJ, Ly M, Bomalaski J, Johnston A, Lin C-C, Chao Y, Chen L-T (2018) Phase III randomized study of second line ADI-PEG 20 plus best supportive care versus placebo plus best supportive care in patients with advanced hepatocellular carcinoma. Ann Oncol 29: 1402–1408. https://doi.org/10.1093/annonc/mdy101
  31. Wei J, Bera TK, Liu XF, Zhou Q, Onda M, Ho M, Tai C-H, Pastan I (2018) Recombinant immunotoxins with albumin-binding domains have long half-lives and high antitumor activity. Proc Natl Acad Sci U S A 115: E3501–E3508. https://doi.org/10.1073/pnas.1721780115
  32. Li R, Yang H, Jia D, Nie Q, Cai H, Fan Q, Wan L, Li L, Lu X (2016) Fusion to an albumin-binding domain with a high affinity for albumin extends the circulatory half-life and enhances the in vivo antitumor effects of human TRAIL. J Control Release 228: 96–106. https://doi.org/10.1016/j.jconrel.2016.03.004
  33. Changou CA, Chen Y-R, Xing L, Yen Y, Chuang FYS, Cheng RH, Bold RJ, Ann DK, Kung H-J (2014) Arginine starvation-associated atypical cellular death involves mitochondrial dysfunction, nuclear DNA leakage, and chromatin autophagy. Proc Natl Acad Sci U S A 111: 14147–14152. https://doi.org/10.1073/pnas.1404171111
  34. Izzo F, Marra P, Beneduce G, Castello G, Vallone P, De Rosa V, Cremona F, Ensor CM, Holtsberg FW, Bomalaski JS, Clark MA, Ng C, Curley SA (2004) Pegylated arginine deiminase treatment of patients with unresectable hepatocellular carcinoma: results from phase I/II studies. J Clin Oncol 22: 1815–1822. https://doi.org/10.1200/JCO.2004.11.120
  35. Feun LG, Marini A, Walker G, Elgart G, Moffat F, Rodgers SE, Wu CJ, You M, Wangpaichitr M, Kuo MT, Sisson W, Jungbluth AA, Bomalaski J, Savaraj N (2012) Negative argininosuccinate synthetase expression in melanoma tumours may predict clinical benefit from arginine-depleting therapy with pegylated arginine deiminase. Br J Cancer 106: 1481–1485. https://doi.org/10.1038/bjc.2012.106
  36. Syed N, Langer J, Janczar K, Singh P, Lo Nigro C, Lattanzio L, Coley HM, Hatzimichael E, Bomalaski J, Szlosarek P, Awad M, O’Neil K, Roncaroli F, Crook T (2013) Epigenetic status of argininosuccinate synthetase and argininosuccinate lyase modulates autophagy and cell death in glioblastoma. Cell Death Dis 4: e458. https://doi.org/10.1038/cddis.2012.197
  37. Savaraj N, Wu C, Li Y-Y, Wangpaichitr M, You M, Bomalaski J, He W, Kuo MT, Feun LG (2015) Targeting argininosuccinate synthetase negative melanomas using combination of arginine degrading enzyme and cisplatin. Oncotarget 6: 6295–6309.
  38. Starikova EA, Sokolov AV, Vlasenko AY, Burova LA, Freidlin IS, Vasilyev VB (2016) Biochemical and biological activity of arginine deiminase from Streptococcus pyogenes M22. Biochem Cell Biol 94: 129–137. https://doi.org/10.1139/bcb-2015-0069
  39. Starikova EA, Golovin AS, Vasilyev KA, Karaseva AB, Serebriakova MK, Sokolov AV, Kudryavtsev IV, Burova LA, Voynova IV, Suvorov AN, Vasilyev VB, Freidlin IS (2019) Role of arginine deiminase in thymic atrophy during experimental Streptococcus pyogenes infection. Scand J Immunol 89: e12734. https://doi.org/10.1111/sji.12734
  40. Ding L, Cao J, Lin W, Chen H, Xiong X, Ao H, Yu M, Lin J, Cui Q (2020) The Roles of Cyclin-Dependent Kinases in Cell-Cycle Progression and Therapeutic Strategies in Human Breast Cancer. Int J Mol Sci 21: 1960. https://doi.org/10.3390/ijms21061960
  41. He L, Zhang J, Zhao J, Ma N, Kim SW, Qiao S, Ma X (2018) Autophagy: The Last Defense against Cellular Nutritional Stress. Adv Nutr 9: 493–504. https://doi.org/10.1093/advances/nmy011
  42. Chikte S, Panchal N, Warnes G (2014) Use of LysoTracker dyes: A flow cytometric study of autophagy. Cytometry Part A 85: 169–178. https://doi.org/10.1002/cyto.a.22312
  43. Gong H, Zölzer F, von Recklinghausen G, Havers W, Schweigerer L (2000) Arginine deiminase inhibits proliferation of human leukemia cells more potently than asparaginase by inducing cell cycle arrest and apoptosis. Leukemia 14: 826–829. https://doi.org/10.1038/sj.leu.2401763
  44. Taheri F, Ochoa JB, Faghiri Z, Culotta K, Park HJ, Lan MS, Zea AH, Ochoa AC (2001) L-Arginine regulates the expression of the T-cell receptor zeta chain (CD3zeta) in Jurkat cells. Clin Cancer Res 7: 958s–965s.
  45. Unissa R, Sudhakar M, Reddy ASK (2016) Evaluation of in vitro Anti-proliferative Activity of L‑arginine deiminase from Novel Marine Bacterial Isolate. Microbiol Res J Int 1–10. https://doi.org/10.9734/BMRJ/2016/23592
  46. García-Navas R, Munder M, Mollinedo F (2012) Depletion of L-arginine induces autophagy as a cytoprotective response to endoplasmic reticulum stress in human T lymphocytes. Autophagy 8: 1557–1576. https://doi.org/10.4161/auto.21315
  47. Di Marzio L, Russo FP, D’Alò S, Biordi L, Ulisse S, Amicosante G, De Simone C, Cifone MG (2001) Apoptotic effects of selected strains of lactic acid bacteria on a human T leukemia cell line are associated with bacterial arginine deiminase and/or sphingomyelinase activities. Nutr Cancer 40: 185–196. https://doi.org/10.1207/S15327914NC402_16

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Copyright (c) 2023 Э.А. Старикова, Дж.Т. Маммедова, А. Ожиганова, Л.А. Бурова, И.В. Кудрявцев