AURUM POLYACRYLATE: THE EXPERIMENTAL STUDY OF THE ANTITUMOR ACTIVITY

Introduction. The investigation of metal substituted organic compounds as potential antitumor drugs is one of the promising areas of research in experimental and clinical oncology.

Objective. The pre-clinical study of the original antitumor drug aurum polyacrylate (aurumacryl) which belongs to such new for oncology group of compounds as polyacrylates of metals was the aim of this work.

Materials and methods.  Aurumacryl antitumor activity was determined as the tumor growth inhibitory effect against some of the murine solid tumors (Lewis lung carcinoma, Acatol adenocarcinoma and Ca-755 adenocarcinoma). Drug cytotoxic effect against some of the human tumor cells (Mel-Mo melanoma, A549 lung carcinoma, MCF-7 breast carcinoma, HCT116 colon adenocarcinoma) was evaluated with standard МТТ-test. The aurumacryl pharmacokinetics in tumor bearing mice (Lewis lung carcinoma) was studied. The inductively coupled plasma mass spectrometry method was used for the estimation of the aurum maintenance in the tested tissues (tumor, blood, kidneys, liver, lungs, spleen, brain).

Results. The 80–90 % tumor growth inhibitory effect of aurumacryl against some solid tumors in mice had been revealed in vivo as well as the death of the 60–90 % human tumor cells of various origins in vitro. Beside this the strong decrease of the number of proliferating MCF-7 tumor cells had been shown. The distribution of aurumacryl in the body of the mice with the solid tumor had been revealed.

Conclusion. On the base of the data obtained the further study of the aurumacryl as a potential antitumor agent seems rather promising.

1. Babin V.N., Belousov Yu.A., Borisov V.I. et al. Ferrocenes as potential anticancer drugs. Facts and hypotheses.(Review). Izv. RAN Ser. khim = Russian Chemical Bulletin 2014;63(11):2405–22. (In Russ.).

2. Korman D. B. The Basics of Antitumor Chemotherapy. Moscow: Prakticheskaya meditsina, 2006. 503 р. (In Russ.).

3. Markowska A., Kasprzak B., Jaszczynska-Nowinka K. et al. Nobel metals in oncology. Contemp Oncol (Pozn) 2015;19:271–5. DOI: 10.5114/wo.2015.54386.

4. Da Silva Maia P.I., Deflon V.M., Abram U. Gold (III) complexes in medicinal chemistry. Future Med Chem 2014;6:1515–36. DOI: 10.4155/fmc.14.87.

5. Nardon C., Pettenuzzo N., Fregona D. Gold complexes for therapeutic purpose: an update patent review (2010–2015). Curr Med Chem 2016;23:3374–403. DOI: 10.2174/0929867323666160504103843.

6. Nobili S., Mini E., Landini I. et al. Gold compounds as anticancer agents: chemistry, cellular pharmacology and preclinical studies. Med Res Rev 2010;30(3):550–80. DOI: 10.1002/med.20168.

7. Korman D.B., Ostrovskaya L.A., Kuz’min V.A. Gold complexes – antitumor properties, targets and mechanism of action (An Overview). Voprosy onkologii = Problems in oncology 2018;64(6):697–707. (In Russ.).

8. Korman D.B., Ostrovskaya L.A., Kuz’min V.A. Induction of Oxidative Stress in Tumor Cells: A New Strategy for Drug Therapy of Malignant Tumors(An Overview). Biophizika = Biophysics 2019;64(3):552–62. (In Russ.).

9. Ostrovskaya L.A., Voronkov M.G., Korman D.B. et al. Experimental Study of Antitumor Activity of Polymetalacrylates against Animal TrasplantableTumors. J оf Cancer Therapy 2010;1(2):59–65. DOI: 10.4236/jct.2010.12010.

10. Ostrovskaya L.A., Korman D.B., Bluhterova N.V. et al. Antitumor Activity of Polyacrylates of Noble Metals in Experiment. Biointerface Research in Applied Chemistry 2014;4:816–9.

11. Ostrovskaya L.A., Voronkov M.G., Korman D.B. et al. Polyacrylates of Noble Metals as Potential Antitumor Drugs. Biophizika = Biophysics 2014;59(4):785–89. (In Russ.).

12. Ostrovskaya L.A., Varfolomeev S.D., Voronkov M.G. et al. Polymetalacrylates, ferrocene compounds, polysuccinimide as potential antitumor drugs. Izv. RAN Ser. khim. = Russian Chemical Bulletin 2014;5:1211–8. (In Russ.).

13. Ostrovskaya L.A., Grehova A.K., Korman D.B. et al. Experimental study of the antitumor effect of aurumacryl. Izv. RAN Ser. khim. = Russian Chemical Bulletin 2017;66(12):2333–7. (In Russ.).

14. Ostrovskaya L.A., Grehova A.K., Korman D.B. et al. Cellular Effects of the Antitumor Drug Aurumacryl. Biophizika = Biophysics 2017;62(3):598–603. (In Russ.).

15. Ostrovskaya L.A., Korman D.B., Bluhterova N.V. et al. Рolyacrylates of metals are the new class of the potential antitumor drugs. Khimicheskaya phizika = Russ J Phys Chem B 2019;38(12):64–73. (In Russ.).

16. Smirnova M.S., Spiridonov V.V., Pozdniakova N.V. et al. Method of producing gold polyacrylate exhibiting anti-tumor activity. RF Patent of Invention № 2690536 from 04.06.2019. (In Russ.).

17. Treschalina E.M., Zhukova O.S., Gerasimova G.K. et al. Guidelines for Preclinical Study of Pharmacological Substances. Part one. (Ed. by A.N. Mironov). Moscow: Griff i K. 2012. Pp. 642–57. (In Russ.).

18. Korman D.B., Nekrasova E.I., Ostrovskaya L.A. et al. The sensitivity of human tumor cells to the cytotoxic action of aurum polyacrylate (aurumacril). Biophizika = Biophysics 2019;64(6):1138–45 . (In Russ.).

19. Ostrovskaya L.A., Korman D.B., Burmiy J.P. et al. An Experimental Study of the Pharmacokinetics of the Antitumor Drug Aurumacryl. Biophizika = Biophysics 2018;63(3):606–14. (In Russ.).

20. Karandashev V.K., Orlova T.A., Lezhnev A.E. et al. Use of the inductively coupled plasma mass spectrometry for element analysis of environmental objects. Inorganic Materials 2008;44(14):1491–1500. DOI: 10.1134/S0020168508140045.

21. Abzaeva K.A., Zhilitskaya L.V., Belozerskaya G.G. et al. Effect of the metal nature on hemostatic activity of water-soluble gold and silver nanocomposites. Izv RAN Ser khim = Russian Chemical Bulletin 2017;66(12): 2314–6. (In Russ.).

22. Ranconi L., Aldinucoi D.P., Fregona D. Latest insights into anticancer activity of gold(III)-dithiocarbamato complexes. Anti-Cancer Agents in Med Chem 2010;(4):283–92. DOI: 10.2174/187152010791162298/.

23. Saggioro D., Rigobello M.P., Paloschi L. et al. Gold (III)-dithiocarbamato complexes induce cancer cell death triggered by thioredoxin redox system inhibition and activation of ERK pathway. Chemistry & Biology 2007;14:1128–39. DOI: 10.1016/j.chembiol.2007.08.016.

24. Casini A., Messori L. Molecular mechanisms and proposed targets for selected anticancer gold compounds. Curr Top Med Chem 2011;11:2647–60. DOI: 10.2174/156802611798040732.

25. Zapadinskii B.I., Kotova A.V., Matveeva I.A. et al. Uv radiation induced formation of gold nanoparticles in threedimensional. Khimicheskaya phizika = Russ J Phys Chem B 2010;29(10):87–97. (In Russ.).

26. Plate N.A., Vasilyev A.E. Physiologically Active Polymers. Moscow: Khimiya, 1986. 293 р. (In Russ.).