Skip to main content

Advertisement

SpringerLink
Log in

Ruthenium (II)/allopurinol complex inhibits breast cancer progression via multiple targets

  • Original Paper
  • Published:
JBIC Journal of Biological Inorganic Chemistry Aims and scope Submit manuscript

Abstract

Metal complexes based on ruthenium have established excellent activity with less toxicity and great selectivity for tumor cells. This study aims to assess the anticancer potential of ruthenium(II)/allopurinol complexes called [RuCl2(allo)2(PPh3)2] (1) and [RuCl2(allo)2(dppb)] (2), where allo means allopurinol, PPh3 is triphenylphosphine and dppb, 1,4-bis(diphenylphosphino)butane. The complexes were synthesized and characterized by elemental analysis, IR, UV–Vis and NMR spectroscopies, cyclic voltammetry, molar conductance measurements, as well as the X-ray crystallographic analysis of complex 2. The antitumor effects of compounds were determined by cytotoxic activity and cellular and molecular responses to cell death mechanisms. Complex 2 showed good antitumor profile prospects because in addition to its cytotoxicity, it causes cell cycle arrest, induction of DNA damage, morphological and biochemical alterations in the cells. Moreover, complex 2 induces cell death by p53-mediated apoptosis, caspase activation, increased Beclin-1 levels and decreased ROS levels. Therefore, complex 2 can be considered a suitable compound in antitumor treatment due to its cytotoxic mechanism.

Graphic abstract

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Scheme 1
Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  1. Allardyce CS, Dyson PJ (2001) Ruthenium in medicine: current clinical uses and future prospects. Platin Met Rev 2:62

    Google Scholar 

  2. Clarke MJ (2002) Ruthenium metallopharmaceuticals. Coord Chem Rev 262:69–93

    Article  Google Scholar 

  3. Kostova I (2006) Ruthenium complexes as anticancer agents. Curr Med Chem. https://doi.org/10.2174/092986706776360941

    Article  PubMed  Google Scholar 

  4. Naves MA, Graminha AE, Vegas LC et al (2019) Transport of the ruthenium complex [Ru(GA)(dppe) 2 ]PF 6 into triple-negative breast cancer cells is facilitated by transferrin receptors ̃. Mol Pharm. https://doi.org/10.1021/acs.molpharmaceut.8b01154

    Article  PubMed  Google Scholar 

  5. de Pereira FC, Lima BAV, de Lima AP et al (2015) Cis-[RuCl(BzCN)(N–N)(P–P)]PF6 complexes: synthesis and in vitro antitumor activity. J Inorg Biochem 149:91–101. https://doi.org/10.1016/j.jinorgbio.2015.03.011

    Article  CAS  Google Scholar 

  6. Takarada JE, Guedes APM, Correa RS et al (2017) Ru/Fe bimetallic complexes: synthesis, characterization, cytotoxicity and study of their interactions with DNA/HSA and human topoisomerase IB. Arch Biochem Biophys 636:28–41. https://doi.org/10.1016/j.abb.2017.10.015

    Article  CAS  PubMed  Google Scholar 

  7. Guedes A, Mello-Andrade F, Pires W, de Sousa M, da Silva P, de Camargo M, Gemeiner H, Amauri M, Gomes Cardoso C, de Melo RP, Silveira-Lacerda E, Batista A (2020) Heterobimetallic Ru(ii)/Fe(ii) complexes as potent anticancer agents against breast cancer cells, inducing apoptosis through multiple targets. Meta Gene. https://doi.org/10.1039/C9MT00272C

    Article  Google Scholar 

  8. Mello-Andrade F, da Costa WL, Pires WC et al (2017) Antitumor effectiveness and mechanism of action of Ru(II)/amino acid/diphosphine complexes in the peritoneal carcinomatosis progression. Tumor Biol. https://doi.org/10.1177/1010428317695933

    Article  Google Scholar 

  9. Mello-Andrade F, Cardoso CG, Silva CR et al (2018) Acute toxic effects of ruthenium (II)/amino acid/diphosphine complexes on Swiss mice and zebrafish embryos. Biomed Pharmacother 107:1082–1092. https://doi.org/10.1016/j.biopha.2018.08.051

    Article  CAS  PubMed  Google Scholar 

  10. Velozo-Sá VS, Pereira LR, Lima AP et al (2019) In vitro cytotoxicity and in vivo zebrafish toxicity evaluation of Ru(ii)/2-mercaptopyrimidine complexes. Dalt Trans 48:6026–6039. https://doi.org/10.1039/c8dt03738h

    Article  CAS  Google Scholar 

  11. Pacher P, Nivorozhkin A, Szabó C (2006) Therapeutic effects of xanthine oxidase inhibitors: renaissance half a century after the discovery of allopurinol. Pharmacol Rev 58:87–114

    Article  CAS  Google Scholar 

  12. Giamanco NM, Cunningham BS, Klein LS et al (2016) Allopurinol use during maintenance therapy for acute lymphoblastic leukemia avoids mercaptopurine-related hepatotoxicity. J Pediatr Hematol Oncol. https://doi.org/10.1097/MPH.0000000000000499

    Article  PubMed  Google Scholar 

  13. Sewani HH, Rabatin JT (2002) Acute tumor lysis syndrome in a patient with mixed small cell and non-small cell tumor. Mayo Clin Proc. https://doi.org/10.4065/77.7.722

    Article  PubMed  Google Scholar 

  14. Czupryna J, Tsourkas A (2012) Xanthine oxidase-generated hydrogen peroxide is a consequence, not a mediator of cell death. FEBS J. https://doi.org/10.1111/j.1742-4658.2012.08475.x

    Article  PubMed  Google Scholar 

  15. Rodrigues MVN, Corrêa RS, Vanzolini KL et al (2015) Characterization and screening of tight binding inhibitors of xanthine oxidase: an on-flow assay. RSC Adv. https://doi.org/10.1039/c5ra01741f

    Article  Google Scholar 

  16. Battelli MG, Polito L, Bortolotti M, Bolognesi A (2016) Xanthine oxidoreductase-derived reactive species: physiological and pathological effects. Oxid Med Cell Longev. https://doi.org/10.1155/2016/3527579

    Article  PubMed  Google Scholar 

  17. Wolfe A, Shimer GH, Meehan T (1987) Polycyclic aromatic hydrocarbons physically intercalate into duplex regions of denatured DNA. Biochemistry. https://doi.org/10.1021/bi00394a013

    Article  PubMed  Google Scholar 

  18. Mosmann T (1983) Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods. https://doi.org/10.1016/0022-1759(83)90303-4

    Article  PubMed  Google Scholar 

  19. Rafehi H, Orlowski C, Georgiadis GT et al (2011) Clonogenic assay: adherent cells. J Vis Exp. https://doi.org/10.3791/2573

    Article  PubMed  PubMed Central  Google Scholar 

  20. Gebäck T, Schulz MMP, Koumoutsakos P, Detmar M (2009) TScratch: a novel and simple software tool for automated analysis of monolayer wound healing assays. Biotechniques. https://doi.org/10.2144/000113083

    Article  PubMed  Google Scholar 

  21. Azqueta A, Collins AR (2013) The essential comet assay: a comprehensive guide to measuring DNA damage and repair. Arch Toxicol 87:949–968

    Article  CAS  Google Scholar 

  22. de Lima AP, Pereira FC, Vilanova-Costa, CAST et al (2014) The ruthenium complex cis-(dichloro)tetrammineruthenium(III) chloride induces apoptosis and damages DNA in murine sarcoma 180 cells. J Biosci. https://doi.org/10.1007/s12038-010-0042-2

    Article  Google Scholar 

  23. Kobayashi H, Sugiyama C, Morikawa Y, et al (1995) A comparison between manual microscopic analysis and computerized image analysis in the single cell gel electrophoresis assay.

  24. Carlisi D, Buttitta G, Di Fiore R et al (2016) Parthenolide and DMAPT exert cytotoxic effects on breast cancer stem-like cells by inducing oxidative stress, mitochondrial dysfunction and necrosis. Cell Death Dis. https://doi.org/10.1038/cddis.2016.94

    Article  PubMed  PubMed Central  Google Scholar 

  25. Aubry JP, Blaecke A, Lecoanet-Henchoz S et al (1999) Annexin V used for measuring apoptosis in the early events of cellular cytotoxicity. Cytometry. https://doi.org/10.1002/(SICI)1097-0320(19991101)37:3%3c197::AID-CYTO6%3e3.0.CO;2-L

    Article  PubMed  Google Scholar 

  26. Yang X, Feng Y, Liu Y et al (2014) A quantitative method for measurement of HL-60 cell apoptosis based on diffraction imaging flow cytometry technique. Biomed Opt Express. https://doi.org/10.1364/boe.5.002172

    Article  PubMed  PubMed Central  Google Scholar 

  27. Pietkiewicz S, Schmidt JH, Lavrik IN (2015) Quantification of apoptosis and necroptosis at the single cell level by a combination of Imaging Flow Cytometry with classical Annexin V/propidium iodide staining. J Immunol Methods. https://doi.org/10.1016/j.jim.2015.04.025

    Article  PubMed  Google Scholar 

  28. Majno G, Joris I (1995) Apoptosis, oncosis, and necrosis: an overview of cell death. Am J Pathol 146:3–15

    CAS  PubMed  PubMed Central  Google Scholar 

  29. Matassov D, Kagan T, Leblanc J et al (2004) Measurement of apoptosis by DNA fragmentation. Methods Mol Biol. https://doi.org/10.1385/1-59259-812-9:001

    Article  PubMed  Google Scholar 

  30. Silva MT (2010) Secondary necrosis: the natural outcome of the complete apoptotic program. FEBS Lett 22:4491–4499

    Article  Google Scholar 

  31. Poon IKH, Hulett MD, Parish CR (2010) Molecular mechanisms of late apoptotic/necrotic cell clearance. Cell Death Differ 17:381–397

    Article  CAS  Google Scholar 

  32. Galluzzi L, Vitale I, Abrams JM et al (2012) Molecular definitions of cell death subroutines: recommendations of the nomenclature committee on cell death 2012. Cell Death Differ 19:107–120. https://doi.org/10.1038/cdd.2011.96

    Article  CAS  PubMed  Google Scholar 

  33. Elmore SA, Dixon D, Hailey JR et al (2016) Recommendations from the INHAND apoptosis/necrosis working group. Toxicol Pathol. https://doi.org/10.1177/0192623315625859

    Article  PubMed  PubMed Central  Google Scholar 

  34. Fairbairn DW, Walburger DK, Fairbairn JJ, O’Neill KL (1996) Key morphologic changes and DNA strand breaks in human lymphoid cells: discriminating apoptosis from necrosis. Scanning. https://doi.org/10.1002/sca.1996.4950180603

    Article  PubMed  Google Scholar 

  35. Bastian AM, Yogesh TL, Kumaraswamy KL (2013) Various methods available for detection of apoptotic cells—a review. Indian J Cancer 50:274

    Article  Google Scholar 

  36. Koopman G, Reutelingsperger CPM, Kuijten GAM et al (1994) Annexin V for flow cytometric detection of phosphatidylserine expression on B cells undergoing apoptosis. Blood. https://doi.org/10.1182/blood.v84.5.1415.bloodjournal8451415

    Article  PubMed  Google Scholar 

  37. Balvan J, Krizova A, Gumulec J et al (2015) Multimodal holographic microscopy: distinction between apoptosis and oncosis. PLoS ONE. https://doi.org/10.1371/journal.pone.0121674

    Article  PubMed  PubMed Central  Google Scholar 

  38. Porto HKP, Vilanova-Costa CAST, Dos Santos Mello FM et al (2015) Synthesis of a ruthenium(II) tryptophan-associated complex and biological evaluation against Ehrlich murine breast carcinoma. Transit Met Chem 40:1–10. https://doi.org/10.1007/s11243-014-9882-1

    Article  CAS  Google Scholar 

  39. Popolin CP, Reis JPB, Becceneri AB et al (2017) Cytotoxicity and anti-tumor effects of new ruthenium complexes on triple negative breast cancer cells. PLoS ONE 12:e0183275. https://doi.org/10.1371/journal.pone.0183275

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Magalhães LF, Mello-Andrade F, Pires WC et al (2017) cis -[RuCl(BzCN)(bipy)(dppe)]PF6 induces anti-angiogenesis and apoptosis by a mechanism of caspase-dependent involving DNA damage, PARP activation, and Tp53 induction in Ehrlich tumor cells. Chem Biol Interact 278:101–113. https://doi.org/10.1016/j.cbi.2017.09.013

    Article  CAS  PubMed  Google Scholar 

  41. Pires WC, Lima BAV, de Castro PF et al (2018) Ru(II)/diphenylphosphine/pyridine-6-thiolate complexes induce S-180 cell apoptosis through intrinsic mitochondrial pathway involving inhibition of Bcl-2 and p53/Bax activation. Mol Cell Biochem. https://doi.org/10.1007/s11010-017-3129-3

    Article  PubMed  Google Scholar 

  42. Colina-Vegas L, Luna-Dulcey L, Plutín AM et al (2017) Half sandwich Ru( <scp>ii</scp> )-acylthiourea complexes: DNA/HSA-binding, anti-migration and cell death in a human breast tumor cell line. Dalt Trans. https://doi.org/10.1039/C7DT01801K

    Article  Google Scholar 

  43. Queiroz SL, Batista AA, Oliva G et al (1998) The reactivity of five-coordinate Ru(II) (1,4-bis(diphenylphosphino)butane) complexes with the N-donor ligands: ammonia, pyridine, 4-substituted pyridines, 2,2′-bipyridine, bis(o-pyridyl)amine, 1,10-phenanthroline, 4,7-diphenylphenanthroline and ethylened. Inorgan Chim Acta. https://doi.org/10.1016/s0020-1693(97)05615-6

    Article  Google Scholar 

  44. Hänggi G, Schmalle H, Dubler E (1988) Synthesis and characterization of N(8)-coordinated metal complexes of the anti-hyperuricemia drug allopurinol: Bis(allopurinol)triaqua(sulfato)metal(II) hydrates (Metal = Co, Ni, Zi, Cd). Inorg Chem 27:3131–3137. https://doi.org/10.1021/ic00291a016

    Article  Google Scholar 

  45. Prusiner P, Sundaralingam M (1972) Stereochemistry of nucleic acids and their constituents. XXV. Crystal and molecular structure of adenine N1-oxide–sulfuric acid complex. Acta Crystallogr Sect B Struct Crystallogr Cryst Chem. https://doi.org/10.1107/s0567740872005680

    Article  Google Scholar 

  46. Ganeshpandian M, Loganathan R, Ramakrishnan S et al (2013) Interaction of mixed ligand copper(II) complexes with CT DNA and BSA: effect of primary ligand hydrophobicity on DNA and protein binding and cleavage and anticancer activities. Polyhedron. https://doi.org/10.1016/j.poly.2012.07.021

    Article  Google Scholar 

  47. Loganathan R, Ramakrishnan S, Suresh E et al (2012) Mixed ligand copper(II) complexes of N, N-bis(benzimidazol-2-ylmethyl)amine (BBA) with diimine co-ligands: efficient chemical nuclease and protease activities and cytotoxicity. Inorg Chem. https://doi.org/10.1021/ic2017177

    Article  PubMed  Google Scholar 

  48. Chaveerach U, Meenongwa A, Trongpanich Y et al (2010) DNA binding and cleavage behaviors of copper(II) complexes with amidino-O-methylurea and N-methylphenyl-amidino-O-methylurea, and their antibacterial activities. Polyhedron. https://doi.org/10.1016/j.poly.2009.10.031

    Article  Google Scholar 

  49. Kathryn JC, Sireesha VG, Stanley L (2012) Triple negative breast cancer cell lines: one tool in the search for better treatment of triple negative breast cancer. Breast Dis 32:35–48. https://doi.org/10.3233/BD-2010-0307.Triple

    Article  Google Scholar 

  50. Kau P, Nagaraja GM, Zheng H et al (2012) A mouse model for triple-negative breast cancer tumor-initiating cells (TNBC-TICs) exhibits similar aggressive phenotype to the human disease. BMC Cancer 12:120. https://doi.org/10.1186/1471-2407-12-120

    Article  Google Scholar 

  51. Wu Q, He J, Mei W et al (2014) Arene ruthenium( <scp>ii</scp> ) complex, a potent inhibitor against proliferation, migration and invasion of breast cancer cells, reduces stress fibers, focal adhesions and invadopodia. Metallomics 6:2204–2212. https://doi.org/10.1039/C4MT00158C

    Article  CAS  PubMed  Google Scholar 

  52. Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144:646–674

    Article  CAS  Google Scholar 

  53. Curtin NJ (2012) DNA repair dysregulation from cancer driver to therapeutic target. Nat Rev Cancer 12:801–817

    Article  CAS  Google Scholar 

  54. Riccardi C, Nicoletti I (2006) Analysis of apoptosis by propidium iodide staining and flow cytometry. Nat Protoc. https://doi.org/10.1038/nprot.2006.238

    Article  PubMed  Google Scholar 

  55. Foster DA, Yellen P, Xu L, Saqcena M (2010) Regulation of G1 cell cycle progression: distinguishing the restriction point from a nutrient-sensing cell growth checkpoint(s). Genes Cancer 1:1124–1131

    Article  CAS  Google Scholar 

  56. Antonarakis ES, Emadi A (2010) Ruthenium-based chemotherapeutics: are they ready for prime time? Cancer Chemother Pharmacol 66:1–9. https://doi.org/10.1007/s00280-010-1293-1

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Collins AR (2004) The comet assay for DNA damage and repair: principles, applications, and limitations. Appl Biochem Biotechnol Part B Mol Biotechnol 26:249–261

    CAS  Google Scholar 

  58. Saikolappan S, Kumar B, Shishodia G et al (2019) Reactive oxygen species and cancer: a complex interaction. Cancer Lett 452:132–143

    Article  CAS  Google Scholar 

  59. Srinivas US, Tan BWQ, Vellayappan BA, Jeyasekharan AD (2019) ROS and the DNA damage response in cancer. Redox Biol 25:101084

    Article  CAS  Google Scholar 

  60. Ma Y, Chapman J, Levine M et al (2014) Cancer: high-dose parenteral ascorbate enhanced chemosensitivity of ovarian cancer and reduced toxicity of chemotherapy. Sci Transl Med. https://doi.org/10.1126/scitranslmed.3007154

    Article  PubMed  PubMed Central  Google Scholar 

  61. Nauman G, Gray JC, Parkinson R et al (2018) Systematic review of intravenous ascorbate in cancer clinical trials. Antioxidants 7:89

    Article  Google Scholar 

  62. Broekman MMTJ, Roelofs HMJ, Wong DR et al (2015) Allopurinol and 5-aminosalicylic acid influence thiopurine-induced hepatotoxicity in vitro. Cell Biol Toxicol. https://doi.org/10.1007/s10565-015-9301-1

    Article  PubMed  PubMed Central  Google Scholar 

  63. Wolbers F, Buijtenhuijs P, Haanen C, Vermes I (2004) Apoptotic cell death kinetics in vitro depend on the cell types and the inducers used. Apoptosis. https://doi.org/10.1023/B:APPT.0000025816.16399.7a

    Article  PubMed  Google Scholar 

  64. Cummings BS, Wills LP, Schnellmann RG (2012) Measurement of cell death in unit 128 mammalian cells. Curr Protoc Pharmacol. https://doi.org/10.1002/0471141755.ph1208s56

    Article  PubMed  Google Scholar 

  65. Mello-Andrade F, da Costa WL, Pires WC et al (2017) Antitumor effectiveness and mechanism of action of Ru(II)/amino acid/diphosphine complexes in the peritoneal carcinomatosis progression. Tumor Biol 39:1–18. https://doi.org/10.1177/1010428317695933

    Article  CAS  Google Scholar 

  66. Pettinari R, Marchetti F, Petrini A et al (2017) Ruthenium(II)-arene complexes with dibenzoylmethane induce apoptotic cell death in multiple myeloma cell lines. Inorganica Chim Acta. https://doi.org/10.1016/j.ica.2016.04.031

    Article  Google Scholar 

  67. Chen D, Zhou Q (2004) Caspase cleavage of BimEL triggers a positive feedback amplification of apoptotic signaling. Proc Natl Acad Sci USA. https://doi.org/10.1073/pnas.0308050100

    Article  PubMed  Google Scholar 

  68. Wirawan E, Vande Walle L, Kersse K et al (2010) Caspase-mediated cleavage of Beclin-1 inactivates Beclin-1-induced autophagy and enhances apoptosis by promoting the release of proapoptotic factors from mitochondria. Cell Death Dis 1:e81

    Article  Google Scholar 

  69. Mariño G, Niso-Santano M, Baehrecke EH, Kroemer G (2014) Self-consumption: the interplay of autophagy and apoptosis. Nat Rev Mol Cell Biol 15:81–94

    Article  Google Scholar 

  70. Djavaheri-Mergny M, Maiuri MC, Kroemer G (2010) Cross talk between apoptosis and autophagy by caspase-mediated cleavage of Beclin 1. Oncogene 29:1717–1719

    Article  CAS  Google Scholar 

  71. Kang R, Zeh HJ, Lotze MT, Tang D (2011) The Beclin 1 network regulates autophagy and apoptosis. Cell Death Differ 18:571–580

    Article  CAS  Google Scholar 

  72. Vaseva AV, Moll UM (2009) The mitochondrial p53 pathway. Biochim Biophys Acta Bioenerg 1787:414–420. https://doi.org/10.1016/j.bbabio.2008.10.005

    Article  CAS  Google Scholar 

  73. Williams AB, Schumacher B (2016) p53 in the DNA-damage-repair process. Cold Spring Harb Perspect Med. https://doi.org/10.1101/cshperspect.a026070

    Article  PubMed  PubMed Central  Google Scholar 

  74. Schuler M, Bossy-Wetzel E, Goldstein JC et al (2000) p53 induces apoptosis by caspase activation through mitochondrial cytochrome c release. J Biol Chem. https://doi.org/10.1074/jbc.275.10.7337

    Article  PubMed  Google Scholar 

  75. Han J, Goldstein LA, Hou W et al (2010) Regulation of mitochondrial apoptotic events by p53-mediated disruption of complexes between antiapoptotic bcl-2 members and bim. J Biol Chem. https://doi.org/10.1074/jbc.M109.081042

    Article  PubMed  PubMed Central  Google Scholar 

  76. Liu J, Xia H, Kim M et al (2011) Beclin1 controls the levels of p53 by regulating the deubiquitination activity of USP10 and USP13. Cell. https://doi.org/10.1016/j.cell.2011.08.037

    Article  PubMed  PubMed Central  Google Scholar 

  77. Aita VM, Liang XH, Murty VVVS et al (1999) Cloning and genomic organization of beclin 1, a candidate tumor suppressor gene on chromosome 17q21. Genomics. https://doi.org/10.1006/geno.1999.5851

    Article  PubMed  Google Scholar 

  78. Liang XH, Jackson S, Seaman M et al (1999) Induction of autophagy and inhibition of tumorigenesis by beclin 1. Nature. https://doi.org/10.1038/45257

    Article  PubMed  Google Scholar 

  79. Xu F, Fang Y, Yan L et al (2017) Nuclear localization of Beclin 1 promotes radiation-induced DNA damage repair independent of autophagy. Sci Rep. https://doi.org/10.1038/srep45385

    Article  PubMed  PubMed Central  Google Scholar 

  80. Akiyama T, Dass CR, Choong PFM (2009) Bim-targeted cancer therapy: a link between drug action and underlying molecular changes. Mol Cancer Ther 8:3173–3180

    Article  CAS  Google Scholar 

  81. Lima AP, Pereira FC, Almeida MAP et al (2014) Cytoxicity and apoptotic mechanism of ruthenium(II) amino acid complexes in sarcoma-180 tumor cells. PLoS One. https://doi.org/10.1371/journal.pone.0105865

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This work was supported by the Brazilian National Counsel of Technological and Scientific Development (CNPq) (Grant numbers 403588/2016-2 and 308370/2017-1) and the Foundation for Research Support of the State of Minas Gerais (FAPEMIG) (Grant number APQ-01674-18).

Author information

Authors and Affiliations

  1. Laboratório de Genética Molecular E Citogenética Humana, sala 213, Departamento de Genética, Instituto de Ciências Biológicas I, Campus Samambaia, Universidade Federal de Goiás, Avenida Esperança, s/n, Cx Postal: 131, Goiânia, Goiás, CEP 74690-900, Brazil

    Ingrid O. Travassos, Francyelli Mello-Andrade, Raíssa P. Caldeira, Wanessa C. Pires, Paula F. F. da Silva & Elisângela P. de Silveira-Lacerda

  2. Department of Chemistry, Federal Institute of Education, Science and Technology of Goiás, Goiânia, Goiás, 74055-110, Brazil

    Francyelli Mello-Andrade

  3. Department of Chemistry, Federal University of Ouro Preto—UFOP, Ouro Preto, MG, 35400-000, Brazil

    Rodrigo S. Correa & Tamara Teixeira

  4. UniEvangelica University Center, Anapolis, GO, 75083-515, Brazil

    Alisson Martins-Oliveira

  5. Department of Chemistry, Federal University of Sao Carlos—UFSCar, Sao Carlos, SP, 13565-905, Brazil

    Alzir. A. Batista

Authors
  1. Ingrid O. Travassos
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Francyelli Mello-Andrade
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Raíssa P. Caldeira
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Wanessa C. Pires
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Paula F. F. da Silva
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Rodrigo S. Correa
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Tamara Teixeira
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Alisson Martins-Oliveira
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Alzir. A. Batista
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Elisângela P. de Silveira-Lacerda
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

IOT: conceptualization, methodology, formal analysis, investigation, writing, and visualization; FM-A: conceptualization, methodology, investigation, writing, and visualization; RPC: investigation and formal analysis; WCP: investigation and formal analysis; PFFdS: investigation and formal analysis; RSC: conceptualization, methodology, formal analysis, investigation, writing, and funding acquisition; TT: methodology, formal analysis, investigation; AM-O: conceptualization, methodology, formal analysis, and writing; AAB: conceptualization, methodology, writing, and resources; EdPS-L: conceptualization, project administration, and resources.

Corresponding author

Correspondence to Elisângela P. de Silveira-Lacerda.

Ethics declarations

Conflict of interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOC 6081 KB)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Travassos, I.O., Mello-Andrade, F., Caldeira, R.P. et al. Ruthenium (II)/allopurinol complex inhibits breast cancer progression via multiple targets. J Biol Inorg Chem 26, 385–401 (2021). https://doi.org/10.1007/s00775-021-01862-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00775-021-01862-y

Keywords

Search

Navigation