The estimation of transport proteins associated with the phenomenon of multidrug resistance (P-glycoprotein and the protein of multidrug resistance - MRP1) amount and the cysteine-containing low-molecular-weight proteins metallothioneins level of expression in donor’s lymphocytes, B-lymphoblastoid cell line IM9 and its subline resistant to fludarabel were conducted. It was found decrease in the ratio of expression of P-glycoprotein to MRP1 in IM9 subline resistant to fludarabel relative to IM9 parental cell line. So, one of the mechanisms contributing to the development of multidrug resistance in the IM9 cell line, equally with increase of MRP1 protein importance, take place cysteine-enriched cytosolic proteins metallothioneins I/II classes activation as was found.
cell line IM9, multidrug resistance proteins P-glycoprotein and MRP1, metallothioneins, anticancer drugs
1. Stavrovskaya A.A., Gens G.P. Nekotorye novye aspekty issledovaniy mnozhestvennoy lekarstvennoy ustoychivosti opuholevyh kletok. Uspehi molekulyarnoy onkologii, 2014, t. 1, № 1, c. 5-11. @@Stavrovskaya A.A., Guens G.P. Multidrug resistance of tumor cells: some new trends in research. Advances in Molecular Oncology, 2014, vol. 1, no. 1, pp. 5-11. (In Russ.)
2. Szakács G., Váradi A., Özvegy-Laczka C., Sarkadi B. The role of ABC transporters in drug absorption, distribution, metabolism, excretion and toxicity (ADME-Tox). Drug Discovery Today, 2008, vol. 13, no. 9-10, pp. 379-393. DOI:https://doi.org/10.1016/j.drudis.2007.12.010.
3. Leslie E.M., Deeley R.G., Cole S.P.C. Multidrug resistance proteins: role of P-glycoprotein, MRP1, MRP2, and BCRP (ABCG2) in tissue defense. Toxicology and Applied Pharmacology, 2005, vol. 204, pp. 216-237. DOI:https://doi.org/10.1016/j.taap.2004.10.012.
4. Meaden E.R., Hoggard P.G., Khoo S.H., Back D.J. Determination of P-gp and MRP1 expression and function in peripheral blood mononuclear cells in vivo. Journal of Immunological Methods, 2002, vol. 262, pp. 159-165. DOI:https://doi.org/10.1016/s0022-1759(02)00020-0.
5. Giraud C., Manceau S., Declèves X., Goffinet F., Morini J., Chappuy H., Batteux F., Chouzenoux S., Yousif S., Scherrmann J.-M., Blanche S., Tréluyer J.-M. In uence of development, HIV infection, and antiretroviral therapies on the gene expression pro les of ABC transporters in human lymphocytes. Journal of Clinical Pharmacology, 2008, vol. 50, pp. 226-230. DOI:https://doi.org/10.1177/0091270009343696.
6. Fukuda Y., Schuetz J.D. ABC transporters and their role in nucleoside and nucleotide drug resistance. Biochemical Pharmacology, 2012, vol. 83, pp. 1073-1083. DOI:https://doi.org/10.1177/0091270009343696.
7. Dean M. The genetics of ATP-binding cassette transporters. Methods in Enzymology, 2005, vol. 400, pp. 409-429. DOI:https://doi.org/10.1016/S0076-6879(05)00024-8.
8. Wartenberg M., Hoffmann E., Schwindt H., Grünheck F., Petros J., Arnold J.R.S., Hescheler J., Sauer H. Reactive oxygen species-linked regulation of the multidrug resistance transporter P-glycoprotein in Nox-1 overexpressing prostate tumor spheroids. FEBS Letters, 2005, vol. 579, pp. 4541-4549. DOI:https://doi.org/10.1016/j.febslet.2005.06.078.
9. Ermakova N.V. Issledovanie modifikacii mnozhestvennoy lekarstvennoy ustoychivosti opuholevyh kletok: avtoref. dis. kand. biol. nauk: 03.00.04; Ros. akad. nauk, In-t teor. i eksperim. biofiziki. M., 2005,18 s. @@Ermakova N.V. Issledovanie modifikacii mnozhestvennoj lekarstvennoj ustojchivosti opuholevyh kletok: avtoref. dis. kand. biol. nauk: 03.00.04; Ros. akad. nauk, In-t teor. i eksperim. biofiziki. M., 2005, 18 p. (In Russ.)
10. Tamashevskiy A.V., Slobozhanina E.I., Goncharova N.V., Hlebko P.V., Svirnovskiy A.I. Okislitel'nyy stress v eritrocitah pri hronicheskom limfocitarnom leykoze, inducirovannyy protivoopuholevymi preparatami. Izvestiya NAN Belarusi. Seriya biologicheskih nauk, 2010, № 3, c. 62-66. @@Tamashevski A.V., Slobozhanina E.I., Goncharova N.V., Khliabkho P.U., Svirnovski A.I. Oxidative stress in lymphocytes at chronic lymphocytic leukemia induced by anticancer drugs. Proceedings of the National Academy of Sciences of Belarus, Biological series, 2010, no. 3, pp. 62-66. (In Russ.)
11. Tamashevskiy A.V., Garmaza Yu.M., Slobozhanina E.I., Svirnovskiy A.I. Transportnaya aktivnost' R-glikoproteina pri izmenenii redoks-balansa v limfocitah cheloveka. Novosti mediko-biologicheskih nauk, 2012, t. 6, № 4, s. 173-182. @@Tamashevski A.V., Harmaza Y.M., Slobozhanina E.I., Svirnovski A.I. Transport activity P-glycoproteins under redox-balance change in human lymphocytes. News of biomedical sciences, 2012, vol. 6, no. 4, pp. 90-95. (In Russ.)
12. Garmaza Yu.M., Tamashevskiy A.V., Slobozhanina E.I. Metallotioneiny mlekopitayuschih: struktura i biologicheskaya rol'. Izvestiya NAN Belarusi. Seriya biologicheskih nauk, 2016, № 1, s. 107-116. @@Harmaza Y.M., Tamashevski A.V., Slobozhanina E.I. Mammalian methalothioneins: structure and biological role. Proceedings of the National academy of sciences of Belarus, 2016, no. 1, pp. 107-116. (In Russ.)
13. Egan P., Drain S., Conway C., Bjourson A.J., Alexander H.D. Towards Stratified Medicine in Plasma Cell Myeloma.International Journal of Molecular Sciences, 2016, vol. 17, no. 10, pp. 1760-1781. DOI: 10.3390/ ijms17101760.
14. Ricci F., Tedeschi A., Morra E., Montillo M. Fludarabine in the treatment of chronic lymphocytic leukemia: a review. Therapeutics and Clinical Risk Management, 2009, vol. 5, pp. 187-207. DOI:https://doi.org/10.2147/tcrm.s3688.
15. Koczor C.A., Torres R.A., Lewis W. The role of transporters in the toxicity of nucleoside and nucleotide analogs. Expert Opinion on Drug Metabolism & Toxicology, 2012, vol. 8, no. 6, pp. 665-676. DOI: 10.1517/ 17425255.2012.680885.
16. Kalinichenko E. Modificirovannye nukleozidy: sintez i perspektivy ispol'zovaniya v kachestve himioterapevticheskih agentov. Nauka i innovacii, 2004, № 9, c. 57-64. @@Kalinichenko E. Modified nucleosides: synthesis and prospects for use as chemotherapeutic agents. Science and Innovations, 2004, no. 9, pp. 57-64. (In Russ.)
17. Jordan M.A., Himes R.H., Wilson L.Comparison of the effects of vinblastine, vincristine, vindesine, and vinepidine on microtubule dynamics and cell in proliferation vitro. Cancer Res., 1985, vol. 45, pp. 2741-2747.
18. Schuetz J.D., Connelly M.C., Sun D. MRP4: A previously unidentified factor in resistance to nucleoside-based antiviral drugs. Nature Medicine, 1999, vol. 5, no. 9, pp. 1048-1051. DOI:https://doi.org/10.1038/12487.
19. Damaraju V.L., Damaraju S., Young J.D., Baldwin S.A., Mackey J., Sawyer M.B., Cass C.E. Nucleoside anticancer drugs: the role of nucleoside transporters in resistance to cancer chemotherapy. Oncogene, 2003, vol. 22, pp. 7524-7536. DOI:https://doi.org/10.1038/sj.onc.1206952.
20. Szakács G., Paterson J.K., Ludwig J.A., Booth-Genthe C., Gottesman M.M. Targeting multidrug resistance in cancer. Nature Rev. Drug Discov., 2006, vol. 5, no. 3, pp. 219-234. DOI:https://doi.org/10.1038/nrd1984.
21. Borst P., Evers R., Kool M., Wijnholds J. A Family of Drug Transporters: the Multidrug Resistance-Associated Proteins. J. Natl. Cancer Inst., 2000, vol. 92, no. 16, pp. 1295-1302. DOI:https://doi.org/10.1093/jnci/92.16.1295.
22. Krizkova S., Fabrik I., Adam V., Hrabeta J., Eckschlager T., Kizek R. Metallothionein - a promising tool for cancer diagnostics. Bratislavske Lekarske Listy, 2009, vol. 110, pp. 93-97.
23. Pedersen M.O., Larsen A., Stoltenberg M., Penkowa M. The role of metallothionein in oncogenesis and cancer prognosis, Progress in Histochemistry and Cytochemistry, 2009, vol. 44, pp. 29-64. DOI:https://doi.org/10.1016/j.proghi.2008.10.001.
24. Moore A., Pinkerton R. Vincristine: can its therapeutic index be enhanced? Pediatr. Blood Cancer, 2009, vol. 53, pp. 1180-1187. DOI:https://doi.org/10.1002/pbc.22161.
25. Koblyakov V.A. Citohrom P-450: Funkcionirovanie i regulyaciya. Biol. membrany, 2003, t. 20, № 3, c. 265-272. @@Kobliakov V.A. Cytochrome P-450: Functions and regulation. Biol. membranes, 2003, vol. 20, no. 3, pp. 265-272. (In Russ.)
26. Cole Susan P.C. Multidrug Resistance Protein 1 (MRP1, ABCC1), a “Multitasking” ATP-binding Cassette (ABC) Transporter. The Journal of Biological Chemistry, 2014, vol. 289, no. 45, pp. 30880-30888. DOI: 10.1074/ jbc.R114.609248.
