Anti-cancer properties of ruthenium compounds: NAMI-A and KP1019

REVIEW ARTICLE

Anti-cancer properties of ruthenium compounds: NAMI-A and KP1019

Michał Juszczak 1 , Magdalena Kluska 1 , Daniel Wysokiński 1 , Katarzyna Woźniak 1

1. Katedra Genetyki Molekularnej, Wydział Biologii i Ochrony Środowiska, Uniwersytet Łódzki,

Published: 2020-02-19
DOI: 10.5604/01.3001.0013.8549
GICID: 01.3001.0013.8549
Available language versions: en pl
Issue: Postepy Hig Med Dosw 2020; 74 : 12-19

 

Abstract

Cancer research is among the key challenges in current medicine and biology. Many decades of investigations have brought measurable benefits in both areas with regard to expanding the knowledge of the molecular mechanism of cancer and developing treatment strategies. Despite that cancers are still among diseases with the highest mortality rate, and cancer treatment is often unsuccessful and connected with severe side effects. The development of therapeutic strategies in both targeting the primary tumor origin and preventing metastasis is largely based on testing newly synthesized chemical agents, including a group of metal-containing complexes. It seems that ruthenium-containing complexes are of high potential in cancer therapy, and our work presents the current data about the application of ruthenium-based complexes − NAMI-A and KP1019 in cancer therapy.

References

  • 1. Abid M., Shamsi F., Azam A.: Ruthenium complexes: An emergingground to the development of metallopharmaceuticals for cancertherapy. Mini Rev. Med. Chem., 2016; 16: 772–786
    Google Scholar
  • 2. Adeel M.M., Qasim M., Ashfaq U.A., Masoud M.S., Rehman M.U.,Qamar M.T., Javed M.R.: Modelling and simulation of mutant allelesof breast cancer metastasis suppressor 1 (BRMS1) gene. Bioinformation,2014; 10: 454–459
    Google Scholar
  • 3. Alessio E.: Thirty years of the drug candidate NAMI‐A and themyths in the field of ruthenium anticancer compounds: A personalperspective. Eur. J. Inorg. Chem., 2017: 1549–1560
    Google Scholar
  • 4. Alessio E., Messori L.: The deceptively similar ruthenium(III) drugcandidates KP1019 and NAMI-A have different actions. What didwe learn in the past 30 years? Met. Ions Life Sci., 2018; 18: 141–170
    Google Scholar
  • 5. Alessio E., Messori L.: NAMI-A and KP1019/1339, two iconic rutheniumanticancer drug candidates face-to-face: A case story inmedicinal inorganic chemistry. Molecules, 2019; 24: 1995
    Google Scholar
  • 6. Anchuri S.S., Thota S., Yerra R., Devarakonda K.P., Dhulipala S.:Novel mononuclear ruthenium(II) compounds in cancer therapy.Asian Pac. J. Cancer Prev., 2012; 13: 3293–3298
    Google Scholar
  • 7. Bergamo A., Masi A., Jakupec M.A., Keppler B.K., Sava G.: Inhibitoryeffects of the ruthenium complex KP1019 in models of mammarycancer cell migration and invasion. Met. Based Drugs, 2009;2009: 681270
    Google Scholar
  • 8. Bergamo A., Messori L., Piccioli F., Cocchietto M., Sava G.: Biologicalrole of adduct formation of the ruthenium(III) complex NAMI–A with serum albumin and serum transferrin. Invest. New Drugs,2003; 21: 401–411
    Google Scholar
  • 9. Bergamo A., Pelillo C., Chambery A., Sava G.: Influence of componentsof tumour microenvironment on the response of HCT-116colorectal cancer to the ruthenium-based drug NAMI-A. J. Inorg.Biochem., 2017; 168: 90–97
    Google Scholar
  • 10. Bierle L.A., Reich K.L., Taylor B.E., Blatt E.B., Middleton S.M., BurkeS.D., Stultz L.K., Hanson P.K., Partridge J.F., Miller M.E.: DNA damage responsecheckpoint activation drives KP1019 dependent pre-anaphasecell cycle delay in S. cerevisiae. PLoS One, 2015; 10: e138085
    Google Scholar
  • 11. Bijelic A., Theiner S., Keppler B.K., Rompel A.: X-ray structureanalysis of indazolium trans-[tetrachlorobis(1h-indazole)ruthenate(iii)] (KP1019) bound to human serum albumin revealstwo ruthenium binding sites and provides insights into the drugbinding mechanism. J. Med. Chem., 2016; 59: 5894–5903
    Google Scholar
  • 12. Brabec V., Kasparkova J.: Ruthenium coordination compounds ofbiological and biomedical significance. DNA binding agents. Coord.Chem. Rev., 2018; 376: 75–94
    Google Scholar
  • 13. Bratsos I., Jedner S., Gianferrara T., Alessio E.: Ruthenium anticancercompounds: challenges and expectations. Chimia, 2007; 61: 692–697
    Google Scholar
  • 14. Brescacin L., Masi A., Sava G., Bergamo A.: Effects of the ruthenium-based drug NAMI-A on the roles played by TGF-β1 in the metastaticprocess. J. Biol. Inorg. Chem., 2015; 20: 1163–1173
    Google Scholar
  • 15. Burris H.A., Bakewell S., Bendell J.C., Infante J., Jones S.F., SpigelD.R., Weiss G.J., Ramanathan R.K., Ogden A., Von Hoff D.: Safety andactivity of IT-139, a ruthenium-based compound, in patients with advancedsolid tumours: a first-in-human, open-label, dose-escalationphase I study with expansion cohort. ESMO Open, 2017; 1: e000154
    Google Scholar
  • 16. Cao Z., Livas T., Kyprianou N.: Anoikis and EMT: Lethal “liaisons”during cancer progression. Crit. Rev. Oncog., 2016; 21: 155–168
    Google Scholar
  • 17. Casini A., Temperini C., Gabbiani C., Supuran C.T., Messori L.:The x-ray structure of the adduct between NAMI-A and carbonicanhydrase provides insights into the reactivity of this metallodrugwith proteins. Chem. Med. Chem., 2010; 5: 1989–1994
    Google Scholar
  • 18. Castellarin A., Zorzet S., Bergamo A., Sava G.: Pharmacologicalactivities of ruthenium complexes related to their NO scavengingproperties. Int. J. Mol. Sci., 2016; 17: E1254
    Google Scholar
  • 19. Caterino M., Herrmann M., Merlino A., Riccardi C., MontesarchioD., Mroginski M.A., Musumeci D., Ruffo F., Paduano L., HildebrandtP., Kozuch J., Vergara A.: On the pH-modulated Ru-based prodrugactivation mechanism. Inorg. Chem., 2019; 58: 1216–1223
    Google Scholar
  • 20. Ciambellotti S., Pratesi A., Severi M., Ferraro G., Alessio E., MerlinoA., Messori L.: The NAMI A-human ferritin system: A biophysicalcharacterization. Dalton Trans., 2018; 47: 11429–11437
    Google Scholar
  • 21. Ciarimboli G.: Membrane transporters as mediators of cisplatinside-effects. Anticancer Res., 2014; 34: 547–550
    Google Scholar
  • 22. Das D., Khan M.S., Barik G., Avasare V., Pal S.: Computational approachto unravel the role of hydrogen bonding in the interactionof NAMI-A with DNA nucleobases and nucleotides. J. Phys. Chem.A., 2018; 122: 8397–8411
    Google Scholar
  • 23. Dwyer B.G., Johnson E., Cazares E., McFarlane Holman K.L., KirkS.R.: Ruthenium anticancer agent KP1019 binds more tightly thanNAMI-A to tRNA Phe. J. Inorg. Biochem., 2018; 182: 177–183
    Google Scholar
  • 24. Fink K., Boratynski L.: Rola metaloproteinaz w modyfikacji macierzyzewnątrzkomórkowej w nowotworowym wzroście inwazyjnym, w przerzutowaniui w angiogenezie. Postępy Hig. Med. Dośw., 2012; 66: 609–628
    Google Scholar
  • 25. Flocke L.S., Trondl R., Jakupec M.A., Keppler B.K.: Molecularmode of action of NKP-1339 – a clinically investigated rutheniumbaseddrug – involves ER- and ROS-related effects in colon carcinomacell lines. Invest. New Drugs, 2016; 34: 261–268
    Google Scholar
  • 26. Gandalovičová A., Rosel D., Fernandes M., Veselý P., HenebergP., Čermák V., Petruželka L., Kumar S., Sanz-Moreno V., Brábek J.:Migrastatics-anti-metastatic and anti-invasion drugs: promises andchallenges. Trends Cancer, 2017; 3: 391–406
    Google Scholar
  • 27. Gasser G., Ott I., Metzler-Nolte N.: Organometallic anticancercompounds. J. Med. Chem., 2011; 54: 3–25
    Google Scholar
  • 28. Golla U., Swagatika S., Chauhan S., Tomar R.S.: A systematic assessmentof chemical, genetic, and epigenetic factors influencing the activityof anticancer drug KP1019 (FFC14A). Oncotarget, 2017; 8: 98426–98454
    Google Scholar
  • 29. Gransbury G.K., Kappen P., Glover C.J., Hughes J.N., Levina A.,Lay P.A., Musgrave I.F., Harris H.H.: Comparison of KP1019 and NAMIAin tumour-mimetic environments. Metallomics, 2016; 8: 762–773
    Google Scholar
  • 30. Groessl M., Tsybin Y.O., Hartinger C.G., Keppler B.K., Dyson P.J.:Ruthenium versus platinum: interactions of anticancer metallodrugswith duplex oligonucleotides characterised by electrosprayionisation mass spectrometry. J. Biol. Inorg. Chem., 2010; 15: 677–688
    Google Scholar
  • 31. Gu L., Li X., Ran Q., Kang C., Lee C., Shen J.: Antimetastatic activity ofnovel ruthenium (III) pyridine complex. Cancer Med., 2016; 5: 2850–2860
    Google Scholar
  • 32. Guo W., Zheng W., Luo Q., Li X., Zhao Y., Xiong S., Wang F.: Transferrinserves as a mediator to deliver organometallic ruthenium(II)anticancer complexes into cells. Inorg. Chem., 2013; 52: 5328–5338
    Google Scholar
  • 33. Hartinger C.G., Jakupec M.A., Zorbas-Seifried S., Groessl M., EggerA., Berger W., Zorbas H., Dyson P.J., Keppler B.K.: KP1019, a new redoxactiveanticancer agent-preclinical development and results of a clinicalphase I study in tumor patients. Chem. Biodivers., 2008; 5: 2140–2155
    Google Scholar
  • 34. Heffeter P., Böck K., Atil B., Reza Hoda M.A., Körner W., Bartel C.,Jungwirth U., Keppler B.K., Micksche M., Berger W., KoellenspergerG.: Intracellular protein binding patterns of the anticancer rutheniumdrugs KP1019 and KP1339. J. Biol. Inorg. Chem., 2010; 15: 737–748
    Google Scholar
  • 35. Hostetter A.A., Miranda M.L., DeRose V.J., McFarlane HolmanK.L.: Ru binding to RNA following treatment with the antimetastaticprodrug NAMI-A in Saccharomyces cerevisiae and in vitro. J. Biol. Inorg.Chem., 2011; 16: 1177–1185
    Google Scholar
  • 36. Kapitza S., Pongratz M., Jakupec M.A., Heffeter P., Berger W.,Lackinger L., Keppler B.K., Marian B.: Heterocyclic complexes ofruthenium(III) induce apoptosis in colorectal carcinoma cells. J.Cancer Res. Clin. Oncol., 2005; 131: 101–110
    Google Scholar
  • 37. Kratz F., Hartmann M., Keppler B., Messori L.: The binding propertiesof two antitumor ruthenium(III) complexes to apotransferrin.J. Biol. Chem., 1994; 269: 2581–2588
    Google Scholar
  • 38. Kratz F., Keppler B.K., Messori L., Smith C., Baker E.N.: Proteinbindingproperties of two antitumour Ru(III) complexes to humanapotransferrin and apolactoferrin. Met. Based Drugs, 1994; 1: 169–173
    Google Scholar
  • 39. Krøigård A.B., Larsen M.J., Lænkholm A.V., Knoop A.S., JensenJ.D., Bak M., Mollenhauer J., Thomassen M., Kruse T.A.: Identificationof metastasis driver genes by massive parallel sequencing of successivesteps of breast cancer progression. PLoS One, 2018; 13: e0189887
    Google Scholar
  • 40. Lazarević T., Rilak A., Bugarčić Z.D.: Platinum, palladium, gold and rutheniumcomplexes as anticancer agents: Current clinical uses, cytotoxicitystudies and future perspectives. Eur. J. Med. Chem., 2017; 142: 8–31
    Google Scholar
  • 41. Liang J., Levina A., Jia J., Kappen P., Glover C., Johannessen B., LayP.A.: Reactivity and transformation of antimetastatic and cytotoxicrhodium(iii)-dimethyl sulfoxide complexes in biological fluids: AnXAS speciation study. Inorg. Chem., 2019; 58: 4880–4893
    Google Scholar
  • 42. Luck A.N., Mason A.B.: Structure and dynamics of drug carriersand their interaction with cellular receptors: Focus on serum transferrin.Adv. Drug Deliv. Rev., 2013; 65: 1012–1019
    Google Scholar
  • 43. Meier-Menches S.M., Gerner C., Berger W., Hartinger C.G., KepplerB.K.: Structure-activity relationships for ruthenium and osmiumanticancer agents-towards clinical development. Chem. Soc. Rev.,2018; 47: 909–928
    Google Scholar
  • 44. Merlino A.: Interactions between proteins and Ru compoundsof medicinal interest: A structural perspective. Coordin. Chem. Rev.,2016; 326: 111–134
    Google Scholar
  • 45. Messori L., Merlino A.: Ruthenium metalation of proteins: theX-ray structure of the complex formed between NAMI-A and henegg white lysozyme. Dalton Trans., 2014; 43: 6128–6131
    Google Scholar
  • 46. Novohradský V., Bergamo A., Cocchietto M., Zajac J., Brabec V.,Mestroni G., Sava G.: Influence of the binding of reduced NAMI-A tohuman serum albumin on the pharmacokinetics and biological activity.Dalton Trans., 2015; 44: 1905–1913
    Google Scholar
  • 47. Nowakowska A., Tarasiuk J.: Procesy inwazji i przerzutowaniakomórek opornych na chemioterapię. Postępy Hig. Med. Dośw., 2017;71: 380–397
    Google Scholar
  • 48. Pelillo C., Mollica H., Eble J.A., Grosche J., Herzog L., Codan B., SavaG., Bergamo A. J.: Inhibition of adhesion, migration and of α5β1 integrinin the HCT-116 colorectal cancer cells treated with the rutheniumdrug NAMI-A. J. Inorg. Biochem., 2016; 160: 225–235
    Google Scholar
  • 49. Peti W., Pieper T., Sommer M., Keppler B.K., Giester G.: Synthesisof tumor-inhibiting complex salts containing the anion transtetrachlorobis(indazole)ruthenate(III) and crystal structure of thetetraphenylphosphonium salt. Eur. J. Inorg. Chem., 1999; 1551–1555
    Google Scholar
  • 50. Pillozzi S., Gasparoli L., Stefanini M., Ristori M., D’Amico M.,Alessio E., Scaletti F., Becchetti A., Arcangeli A., Messori L.: NAMI-A ishighly cytotoxic toward leukaemia cell lines: evidence of inhibitionof KCa 3.1 channels. Dalton Trans., 2014; 43: 12150–12155
    Google Scholar
  • 51. Popper H.H.: Progression and metastasis of lung cancer. CancerMetastasis Rev., 2016; 35: 75–91
    Google Scholar
  • 52. Rademaker-Lakhai J.M., van den Bongard D., Pluim D., BeijnenJ.H., Schellens J.H.: A Phase I and pharmacological study with imidazolium-trans-DMSO-imidazole tetrachlororuthenate, a novel rutheniumanticancer agent. Clin. Cancer Res., 2004; 10: 3717–3727
    Google Scholar
  • 53. Rancoule C., Guy J.B., Vallard A., Ben Mrad M., Rehailia A., MagnéN.: 50th anniversary of cisplatin. Bull. Cancer, 2017; 104: 167–176
    Google Scholar
  • 54. Romero-Canelón I., Sadler P.J.: Next-generation metal anticancercomplexes: multitargeting via redox modulation. Inorg. Chem.,2013; 52: 12276–12291
    Google Scholar
  • 55. Schoenhacker-Alte B., Mohr T., Pirker C., Kryeziu K., Kuhn P.S.,Buck A., Hofmann T., Gerner C., Hermann G., Koellensperger G.,Keppler B.K., Berger W., Heffeter P.: Sensitivity towards the GRP78inhibitor KP1339/IT-139 is characterized by apoptosis induction viacaspase 8 upon disruption of ER homeostasis. Cancer Lett., 2017;404: 79–88
    Google Scholar
  • 56. Seelig M.H., Berger M.R., Keppler B.K.: Antineoplastic activityof three ruthenium derivatives against chemically induced colorectalcarcinoma in rats. J. Cancer Res. Clin. Oncol., 1992; 118: 195–200
    Google Scholar
  • 57. Singh V., Azad G.K., Mandal P., Reddy M.A., Tomar R.S.: Anticancerdrug KP1019 modulates epigenetics and induces DNA damageresponse in Saccharomyces cerevisiae. FEBS Lett., 2014; 588: 1044–1052
    Google Scholar
  • 58. Śliwińska-Hill U., Celmer J.: Związki koordynacyjne rutenu jakoleki w nowoczesnej terapii przeciwnowotworowej. Nowotwory, 2015;65: 517–528
    Google Scholar
  • 59. Thota S., Rodrigues D.A., Crans D.C., Barreiro E.J.: Ru(II) compounds:Next-generation anticancer metallotherapeutics? J. Med.Chem., 2018; 61: 5805–5821
    Google Scholar
  • 60. Webb M.I., Walsby C.J.: Albumin binding and ligand-exchangeprocesses of the Ru(III) anticancer agent NAMI-A and its bis-DMSOanalogue determined by ENDOR spectroscopy. Dalton Trans., 2015;44: 17482–17493
    Google Scholar
  • 61. Winkler G.C., Barle E.L., Galati G., Kluwe W.M.: Functional differentiationof cytotoxic cancer drugs and targeted cancer therapeutics.Regul. Toxicol. Pharmacol., 2014; 70: 46–53
    Google Scholar
  • 62. Yeung K.T., Yang J.: Epithelial-mesenchymal transition in tumormetastasis. Mol. Oncol., 2017; 11: 28–39
    Google Scholar

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