anthracycline antibiotics

Teraphtal (sodium salt of cobalt 4,5-carboxyphthalocyanine) Decreases Sensitivity of Tumor Cells to Anthracycline Antibiotics and Mitoxantrone in Vitro

EXPERIMENTAL STUDIES , , , , , ,

TA Sidorova1, OO Ryabaya1, VV Tatarskii1, DA Khochenkov1, ES Ivanova1, OL Kaliya2

1 NN Blokhin National Medical Cancer Research Center, 24 Kashirskoye sh., Moscow, Russian Federation, 115478

2 State Research Center NIOPIC, 1 bld. 4 B. Sadovaya str., Moscow, Russian Federation, 123995

For correspondence: Tat’yana Aleksandrovna Sidorova, PhD, 24 Kashirskoye sh., Moscow, Russian Federation, 115478; e-mail: tatsid@yahoo.com

For citation: Sidorova TA, Ryabaya ОО, Tatarskii VV, et al. Teraphtal (sodium salt of cobalt 4,5-carboxyphthalocyanine) Decreases Sensitivity of Tumor Cells to Anthracycline Antibiotics and Mitoxantrone in Vitro. Clinical oncohematology. 2018;11(1):10–25.

DOI: 10.21320/2500-2139-2018-11-1-10-25

ABSTRACT

Background. Anthracycline antibiotics (AA) are widely used in clinical oncohematology. As is well known АА cytotoxicity diminishes in the presence of hemin (FePPIX), an endogenous metalloporphyrine.

Aim. To study effect of teraphtal (TPh) and its structural analog FePPIX on cytotoxicity of “anthraquinone” drugs AA and mitoxantrone (MiTOX) in vitro.

Materials & Methods. The study was performed using human leukemia cells of K562 line and HCT 116 adenocarcinoma cell line. TPh ability to prevent AA-induced tumor cell death has been estimated by the following methods: MTT assays, flow cytometry, light microscopy, cytochemical method for determination of b-galactosidase expression using X-Gal substrate, DNA electrophoresis, LDH release, real time RT-PCR, and radiometric method.

Results. In the presence of TPh (10 µM) the AA and MiTOX cytotoxicity diminishes approximately 4- and 20-fold respectively. The TPh protective potency is dependent on the AA chemical structure. In the presence of TPh aclarubicin toxicity remains constant. The TPh/FePPIX protection from the AA cytotoxicity can involve the same mechanism reducing the ability of the cells, including the leukemia tumor cells, to accumulate AA in the presence of modulators. TPh/FePPIX protects human tumor cells from AA-induced death, such as apoptosis, necrosis, and accelerated senescence (АS). АS in K562 leukemia cell line induced by AA + TPh/FePPIX results in cell-suspension-derived-small-cell colonies. Вeclin-lysosomal pathway of autophagy is not engaged in reducing of the AA toxicity of K562 cells in the presence of TPh.

Conclusion. Reducing of the AA toxicity and revival of cell population growth in the presence of TPh/FePPIX should be taken into consideration when using hematoporphyrins and phthalocyanines having a structure similar to TPh as sensitizers in the chemotherapy protocols.

Keywords: anthracycline antibiotics, mitoxantrone, teraphtal, hemin, human tumor cells, drug induced senescence, autophagy.

Received: July 2, 2017

Accepted: November 13, 2017

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REFERENCES

  1. Arcamone FM. Fifty years of chemical research at Farmitalia. Chemistry. 2009;15(32):7774–91. doi: 10.1002/chem.200900292.
  2. Gewirtz DA. A critical evaluation of the mechanisms of action proposed for the antitumor effects of the anthracycline antibiotics adriamycin and daunorubicin. Biochem Pharmacol. 1999;57(7):727–41. doi: 10.1016/s0006-2952(98)00307-4.
  3. Doroshow JH. Anthracycline antibiotic-stimulated superoxide, hydrogen peroxide, and hydroxyl radical production by NADH dehydrogenase. Cancer Res. 1983;43(10):4543–51.
  4. Doroshow JH, Davies KJ. Redox cycling of anthracyclines by cardiac mitochondria. II. Formation of superoxide anion, hydrogen peroxide, and hydroxyl radical. J Biol Chem. 1986;261(7):3068–74.
  5. Demant EJ. Inactivation of cytochrome c oxidase activity in mitochondrial membranes during redox cycling of doxorubicin. Biochem Pharmacol. 1991;41(4):543–52. doi: 10.1016/0006-2952(91)90626-g.
  6. Sinha BK, Mason RP. Is Metabolic Activation of Topoisomerase II Poisons Important In The Mechanism Of Cytotoxicity? J Drug Metab Toxicol. 2015;6(3):186. doi: 10.4172/2157-7609.1000186.
  7. Robinson NC. Functional binding of cardiolipin to cytochrome c oxidase. J Bioenerg Biomembr. 1993;25(2):153–63. doi: 10.1007/bf00762857.
  8. Nicolay K, de Kruijff B. Effects of adriamycin on respiratory chain activities in mitochondria from rat liver, rat heart and bovine heart. Evidence for a preferential inhibition of complex III and IV. Biochimica et Biophysica Acta (BBA) – Bioenergetics. 1987;892(3):320–30. doi: 10.1016/0005-2728(87)90236-2.
  9. Claypool SM, Koehler CM. The complexity of cardiolipin in health and disease. Trends Biochem Sci. 2012;37(1):32–41. doi: 10.1016/j.tibs.2011.09.003.
  10. Paradies G, Paradies V, De Benedictis V, et al. Functional role of cardiolipin in mitochondrial bioenergetics. Biochimica et Biophysica Acta (BBA) – Bioenergetics. 2014;1837(4):408–17. doi: 10.1016/j.bbabio.2013.10.006.
  11. Kagan VE, Bayir HA, Belikova NA, et al. Cytochrome c/cardiolipin relations in mitochondria: a kiss of death. Free Radic Biol Med. 2009;46(11):1439–53. doi: 10.1016/j.freeradbiomed.2009.03.004.
  12. Petrosillo G, Casanova G, Matera M, et al. Interaction of peroxidized cardiolipin with rat-heart mitochondrial membranes: induction of permeability transition and cytochrome c release. FEBS Lett. 2006;580(27):6311–6. doi: 10.1016/j.febslet.2006.10.036.
  13. Frost B-M, Eksborg S, Bjork O, et al. Pharmacokinetics of doxorubicin in children with acute lymphoblastic leukemia: multi-institutional collaborative study. Med Pediatr Oncol. 2002;38(5):329–37. doi: 10.1002/mpo.10052.
  14. Toldo S, Goehe RW, Lotrionte M, et al. Comparative cardiac toxicity of anthracyclines in vitro and in vivo in the mouse. PLoS One. 2013;8(3):e58421. doi: 10.1371/journal.pone.0058421.
  15. Wang Z, Wang J, Xie R, et al. Mitochondria-derived reactive oxygen species play an important role in doxorubicin-induced platelet apoptosis. Int J Mol Sci. 2015;6(5):11087–100. doi: 10.3390/ijms160511087.
  16. Heart EA, Karandrea S, Liang X, et al. Mechanisms of Doxorubicin Toxicity in Pancreatic β-Cells. Toxicol Sci. 2016;152(2):395–405. doi: 10.1093/toxsci/kfw096.
  17. Wu X, Hasinoff BB. The antitumor anthracyclines doxorubicin and daunorubicin do not inhibit cell growth through the formation of iron-mediated reactive oxygen species. Anticancer Drugs. 2005;16(1):93–9. doi: 10.1097/00001813-200501000-00014.
  18. Tarasiuk J, Frezard F, Garnier-Suillerot A, Gattegno L. Anthracycline incorporation in human lymphocytes. Kinetics of uptake and nuclear concentration. Biochim Biophys Acta. 1989;1013(2):109–17. doi: 10.1016/0167-4889(89)90038-4.
  19. Swift LP, Rephaeli A, Nudelman A, et al. Doxorubicin-DNA adducts induce a non-topoisomerase II-mediated form of cell death. Cancer Res. 2006;66(9):4863–71. doi: 10.1158/0008-5472.can-05-3410.
  20. Skladanowski A, Konopa J. Interstrand DNA crosslinking induced by anthracyclines in tumour cells. Biochem Pharmacol. 1994;47(12):2269–78. doi: 10.1016/0006-2952(94)90265-8.
  21. Tewey KM, Rowe TC, Yang L, et al. Adriamycin-induced DNA damage mediated by mammalian DNA topoisomerase II. Science. 1984;226(4673):466–8. doi: 10.1126/science.6093249.
  22. Mordente A, Meucci E, Martorana GE, et al. Topoisomerases and Anthracyclines: Recent Advances and Perspectives in Anticancer Therapy and Prevention of Cardiotoxicity. Curr Med Chem. 2017;24(15):1607–26. doi: 10.2174/0929867323666161214120355.
  23. Hajji N, Mateos S, Pastor N, et al. Induction of genotoxic and cytotoxic damage by aclarubicin, a dual topoisomerase inhibitor. Mutat Res. 2005;583(1):26–35. doi: 10.1016/j.mrgentox.2005.01.012.
  24. Nitiss JL, Pourquier P, Pommier Y. Aclacinomycin A stabilizes topoisomerase I covalent complexes. Cancer Res. 1997;57(20):4564–9.
  25. Bridewell DJ, Finlay GJ, Baguley BC. Differential actions of aclarubicin and doxorubicin: the role of topoisomerase I. Oncol Res. 1997;9(10):535–42.
  26. Bogason A, Bhuiyan H, Masquelier M, et al. Uptake of anthracyclines in vitro and in vivo in acute myeloid leukemia cells in relation to apoptosis and clinical response. Eur J Clin Pharmacol. 2009;65(12):1179–86. doi: 10.1007/s00228-009-0734-4.
  27. Dartsch DC, Schaefer A, Boldt S, et al. Comparison of anthracycline-induced death of human leukemia cells: programmed cell death versus necrosis. Apoptosis. 2002;7(6):537–48. doi: 10.1023/a:1020647211557.
  28. Koceva-Chyla A, Jedrzejczak M, Skierski J, et al. Mechanisms of induction of apoptosis by anthraquinone anticancer drugs aclarubicin and mitoxantrone in comparison with doxorubicin: relation to drug cytotoxicity and caspase-3 activation. Apoptosis. 2005;10(6):1497–514. doi: 10.1007/s10495-005-1540-9.
  29. Chang BD, Broude EV, Dokmanovic M, et al. A senescence-like phenotype distinguishes tumor cells that undergo terminal proliferation arrest after exposure to anticancer agents. Cancer Res. 1999;59(15):3761–7.
  30. te Poele RH, Okorokov AL, Jardine L, et al. DNA damage is able to induce senescence in tumor cells in vitro and in vivo. Cancer Res. 2002;62(6):1876–83.
  31. Czyz M, Jakubowska J, Sztiller-Sikorska M. STI571/doxorubicin concentration-dependent switch for diverse caspase actions in CML cell line K562. Biochem Pharmacol. 2008;75(9):1761–73. doi: 10.1016/j.bcp.2008.02.004.
  32. Yang MY, Lin PM, Liu YC, et al. Induction of cellular senescence by doxorubicin is associated with upregulated miR-375 and induction of autophagy in K562 cells. PLoS One. 2012;7(5):e37205. doi: 10.1371/journal.pone.0037205.
  33. Mayer P, Gorisse MC, Carpentier Y, Desoize B. Effects of aclarubicin on growth, differentiation and apoptosis of tumor cells in vitro. Bull Cancer. 1994;81(8):670–6.
  34. Rogalska A, Koceva-Chyla A, Jozwiak Z. Aclarubicin-induced ROS generation and collapse of mitochondrial membrane potential in human cancer cell lines. Chem Biol Interact. 2008;176(1):58–70. doi: 10.1016/j.cbi.2008.07.002.
  35. Maejima Y, Adachi S, Ito H, et al. Induction of premature senescence in cardiomyocytes by doxorubicin as a novel mechanism of myocardial damage. Aging Cell. 2008;7(2):125–36. doi: 10.1111/j.1474-9726.2007.00358.x.
  36. Sultana R, Di Domenico F, Tseng M, et al. Doxorubicin-induced thymus senescence. J Proteome Res. 2010;9(12):6232–41. doi: 10.1021/pr100465m.
  37. Litwiniec A, Grzanka A, Helmin-Basa A, et al. Features of senescence and cell death induced by doxorubicin in A549 cells: organization and level of selected cytoskeletal proteins. J Cancer Res Clin Oncol. 2010;136(5):717–36. doi: 10.1007/s00432-009-0711-4.
  38. Eom YW, Kim MA, Park SS, et al. Two distinct modes of cell death induced by doxorubicin: apoptosis and cell death through mitotic catastrophe accompanied by senescence-like phenotype. Oncogene. 2005;24(30):4765–77. doi: 10.1038/sj.onc.1208627.
  39. Joyner DE, Bastar JD, Randall RL. Doxorubicin induces cell senescence preferentially over apoptosis in the FU-SY-1 synovial sarcoma cell line. J Orthop Res. 2006;24(6):1163–9. doi: 10.1002/jor.20169.
  40. Zingoni A, Cecere F, Vulpis E, et al. Genotoxic Stress Induces Senescence-Associated ADAM10-Dependent Release of NKG2D MIC Ligands in Multiple Myeloma Cells. J Immunol. 2015;195(2):736–48. doi: 10.4049/jimmunol.1402643.
  41. Dabritz JH, Yu Y, Milanovic M, et al. CD20-Targeting Immunotherapy Promotes Cellular Senescence in B-Cell Lymphoma. Mol Cancer Ther. 2016;15(5):1074–81. doi: 10.1158/1535-7163.MCT-15-0627.
  42. Gewirtz DA, Alotaibi M, Yakovlev VA, Povirk LF. Tumor Cell Recovery from Senescence Induced by Radiation with PARP Inhibition. Radiat Res. 2016;186(4):327–32. doi: 10.1667/rr14437.1.
  43. Glick D, Barth S, Macleod KF. Autophagy: cellular and molecular mechanisms. J Pathol. 2010;221(1):3–12. doi: 10.1002/path.2697.
  44. Kang R, Zeh HJ, Lotze MT, Tang D. The Beclin 1 network regulates autophagy and apoptosis. Cell Death Differ. 2011;18(4):571–80. doi: 10.1038/cdd.2010.191.
  45. Gewirtz DA. Autophagy and senescence in cancer therapy. J Cell Physiol. 2014;229(1):6–9. doi: 10.1002/jcp.24420.
  46. Svensson SP, Lindgren S, Powell W, Green H. Melanin inhibits cytotoxic effects of doxorubicin and daunorubicin in MOLT 4 cells. Pigment Cell Res. 2003;16(4):351–4. doi: 10.1034/j.1600-0749.2003.00030.x.
  47. Heaney ML, Gardner JR, Karasavvas N, et al. Vitamin C antagonizes the cytotoxic effects of antineoplastic drugs. Cancer Res. 2008;68(19):8031–8. doi: 10.1158/0008-5472.can-08-1490.
  48. Tsiftsoglou AS, Wong W, Wheeler C, et al. Prevention of anthracycline-induced cytotoxicity in hemopoietic cells by hemin. Cancer Res. 1986;46(7):3436–40.
  49. Tsiftsoglou AS, Wong W, Robinson SH. Analysis of hemin-induced protection of human hemopoietic cells from the cytotoxic effects of anthracyclines. Cancer Res. 1988;48(13):3566–70.
  50. Papadopoulou LC, Tsiftsoglou AS. Mitochondrial cytochrome c oxidase as a target site for daunomycin in K-562 cells and heart tissue. Cancer Res. 1993;53(5):1072–8.
  51. Papadopoulou LC, Tsiftsoglou AS. Effects of hemin on apoptosis, suppression of cytochrome c oxidase gene expression, and bone-marrow toxicity induced by doxorubicin (adriamycin). Biochem Pharmacol. 1996;52(5):713–22. doi: 10.1016/0006-2952(96)00349-8.
  52. Nagai T, Kikuchi S, Ohmine K, et al. Hemin reduces cellular sensitivity to imatinib and anthracyclins via Nrf2. J Cell Biochem. 2008;104(2):680–91. doi: 10.1002/jcb.21659.
  53. Bohmer RM, Hoffmann K, Morstyn G. Hematoporphyrin derivative and anthracyclines mutually inhibit cellular uptake and toxicity. Cancer Chemother Pharmacol. 1987;20(1):16–20. doi: 10.1007/bf00252953.
  54. Сидорова Т.А., Какпакова Е.С., Власенкова Н.К. и др. Различная реакция на терафтал культивируемых in vitro клеток, экспрессирующих Р-гликопротеин, и клеток, не экспрессирующих этот белок. Цитология. 2001;43:889–90.
    [Sidorova TA, Kakpakova ES, Vlasenkova NK, et al. Differences in teraphtal response of in vitro cultured cells expressing P-glycoprotein and those without this expression. Tsitologiya. 2001;43:889–90. (In Russ)]
  55. Сидорова Т.А., Вагида М.С., Калия О.Л., Герасимова Г.К. Роль каталазы в защите опухолевых клеток от окислительного стресса, индуцированного бинарной каталитической системой «терафтал + аскорбиновая кислота». Клиническая онкогематология. 2014;7(3):282–9.
    [Sidorova TA, Vagida MS, Kaliya OL, Gerasimova GK. Role of catalase in protection of cancer cells from oxidative stress induced by binary catalytic system “teraphtal + ascorbic acid”. Klinicheskaya onkogematologiya. 2014;7(3):282–9. (In Russ)]
  56. Dimri GP, Lee X, Basile G, et al. A biomarker that identifies senescent human cells in culture and in aging skin in vivo. Proc Natl Acad Sci USA. 1995;92(20):9363–7. doi: 10.1073/pnas.92.20.9363.
  57. Ling YH, Priebe W, Perez-Soler R. Apoptosis induced by anthracycline antibiotics in P388 parent and multidrug-resistant cells. Cancer Res. 1993;53(8):1845–52.
  58. Cummings BS, Schnellmann RG. Measurement of cell death in mammalian cells. Curr Protoc Pharmacol. 2004;25(12.8):12.8.1–22. doi: 10.1002/0471141755.ph1208s25.
  59. Pommier Y, Leo E, Zhang H, Marchand C. DNA topoisomerases and their poisoning by anticancer and antibacterial drugs. Chem Biol. 2010;17(5):421–33. doi: 10.1016/j.chembiol.2010.04.012.
  60. Сидорова Т.А., Пятакова Н.В., Северина И.С. и др. Растворимая гуанилатциклаза (рГЦ) в реализации гипотензивного и антиагрегантного эффектов терафтала (ТФ, натриевая соль 4,5-октакарбоксифталоцианина кобальта). Клиническая онкогематология. 2016;9(2):138–47. doi: 10.21320/2500-2139-2016-9-2-138-147.
    [Sidorova TA, Pyatakova NV, Severina IS, et al. Soluble Guanylyl Cyclase (sGC) in Mechanisms of Hypotensive and Antiaggregatory Effects Induced by Teraphtal (TP, sodium salt 4,5-cardoxyphtalocyanin-cobalt). Clinical oncohematology. 2016;9(2):138–47. doi: 10.21320/2500-2139-2016-9-2-138-147. (In Russ)]
  61. Forrest RA, Swift LP, Rephaeli A, et al. Activation of DNA damage response pathways as a consequence of anthracycline-DNA adduct formation. Biochem Pharmacol. 2012;83(12):1602–12. doi: 10.1016/j.bcp.2012.02.026.
  62. Konopa J. G2 block induced by DNA crosslinking agents and its possible consequences. Biochem Pharmacol. 1988;37(12):2303–9. doi: 10.1016/0006-2952(88)90355-3.
  63. Barlogie B, Drewinko B, Johnston DA, Freireich EJ. The effect of adriamycin on the cell cycle traverse of a human lymphoid cell line. Cancer Res. 1976;36(6):1975–9.
  64. Mosieniak G, Sliwinska MA, Alster O, et al. Polyploidy Formation in Doxorubicin-Treated Cancer Cells Can Favor Escape from Senescence. Neoplasia. 2015;17(12):882–93. doi: 10.1016/j.neo.2015.11.008.
  65. Wu PC, Wang Q, Grobman L, et al. Accelerated cellular senescence in solid tumor therapy. Exp Oncol. 2012;34(3):298–305.
  66. Zucker RM, Adams DJ, Bair KW, Elstein KH. Polyploidy induction as a consequence of topoisomerase inhibition. A flow cytometric assessment. Biochem Pharmacol. 1991;42(11):2199–208. doi: 10.1016/0006-2952(91)90357-b.
  67. McGahon AJ, Brown DG, Martin SJ, et al. Downregulation of Bcr-Abl in K562 cells restores susceptibility to apoptosis: characterization of the apoptotic death. Cell Death Differ. 1997;4(2):95–104. doi: 10.1038/sj.cdd.4400213.
  68. Masquelier M, Zhou QF, Gruber A, Vitols S. Relationship between daunorubicin concentration and apoptosis induction in leukemic cells. Biochem Pharmacol. 2004;67(6):1047–56. doi: 10.1016/j.bcp.2003.10.025.
  69. Nagai K, Nagasawa K, Koma M, et al. Contribution of an unidentified sodium-dependent nucleoside transport system to the uptake and cytotoxicity of anthracycline in mouse M5076 ovarian sarcoma cells. Biochem Pharmacol. 2006;71(5):565–73. doi: 10.1016/j.bcp.2005.11.017.
  70. Aniogo EC, George BPA, Abrahamse H. Phthalocyanine induced phototherapy coupled with doxorubicin; a promising novel treatment for breast cancer. Expert Rev Anticancer Ther. 2017;17(8):693–702. doi: 10.1080/14737140.2017.1347505.