Acadesine Triggers Non-apoptotic Death in Tumor Cells

Cover Page

Abstract


We studied the cytotoxicity of acadesine (5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside) for tumor and normal cells of various species and tissue origin. In tumor cells, acadesine triggered non-apoptotic death; the potency of the compound to normal cells was substantially lower. Acadesine was toxic for tumor cells with multidrug resistant phenotypes caused by the transmembrane transporter Р-glycoprotein or lack of proapoptotic p53. Activity of adenosine receptors was required for acadesine-induced cell death, whereas functioning of АМР-dependent protein kinase was not required. A more pronounced cytotoxicity for tumor cells, as well as the non-canonical death mechanism(s), makes acadesine a promising candidate for antitumor therapy.


V. A. Glazunova

Blokhin Cancer Center, Russian Academy of Medical Sciences

Author for correspondence.
Email: gav-83@mail.ru

Russian Federation

K. V. Lobanov

State Research Institute of Genetics and Selection of Industrial Microorganisms

Email: gav-83@mail.ru

Russian Federation

R. S. Shakulov

State Research Institute of Genetics and Selection of Industrial Microorganisms

Email: gav-83@mail.ru

Russian Federation

A. S. Mironov

State Research Institute of Genetics and Selection of Industrial Microorganisms

Email: gav-83@mail.ru

Russian Federation

A. A. Shtil

Blokhin Cancer Center, Russian Academy of Medical Sciences

Email: gav-83@mail.ru

Russian Federation

  1. // Acadesine. AICA Riboside, ARA 100, Arasine, GP 1 110 // Drugs R D 2008, V.9, №3, P.169-175
  2. Jose C., Bellance N., Chatelain EH., Benard G., Nouette-Gaulain K., Rossignol R. // Drugs R D 2012, V.12, P.100-109
  3. Jose C., Hébert-Chatelain E., Bellance N., Larendra A., Su M., Nouette-Gaulain K., Rossignol R. // Biochimica et Biophysica Acta . 2011, №1807, P.707-718
  4. Van Den Neste E., Van Den Berghe G., Bontemps F. // Expert Opin. Investig. Drugs. 2010, V.19, №4, P.571-578
  5. Javaux F., Vincent MF., Wagner DR., Van den Berghe G. // Biochem. J. 1995, V.305, P.913-919
  6. Merrill GF., Kurth EJ., Hardie DG., Winder WW. // Endocrinol. Metab. 1997, V.273, №6, P.1107-1112
  7. Su RY., Chao Y., Chen TY., Huang DY., Lin WW. // Mol Cancer Ther. 2007, V.6, №5, P.1562-1571
  8. Theodoropoulou S., Kolovou PE., Morizane Y., Kayama M., Nicolaou F., Miller JW., Gragoudas E., Ksander BR., Vavvas DG. // FASEB. 2010, V.24, P.2620-2630
  9. Teresa Whei-Mei Fan. // The Handbook of Metabolomics // Methods in Pharmacology and Toxicology. 2012, V.17, P.439-480
  10. Walker J., Jijon HB., Diaz H., Salehi P., Churchill T., Madsen KL. // Biochem. J. 2005, V.385, P.485-491
  11. Campàs C., Santidrián AF., Domingo A., Gil J. // Leukemia. 2005, V.19, P.292-294
  12. López JM., Santidrián AF., Campàs C., Gil J. // Biochem. J. 2003, V.370, P.1027-1032
  13. Guigas B., Sakamoto K., Taleux N., Reyna SM., Musi N., Viollet B., Hue L. // IUBMB Life. 2009, V.61, №1, P.18-26
  14. Lobanov K.V., Errais Lopes L., Korolkova N.V., Tyaglov B.V., Glazunov A.V., Shakulov R.S., Mironov A.S. // Acta Naturae 2011, V.3, №2(9), P.83-93
  15. Lysenkova L.N., Turchin K.F., Korolev A.M., Bykov E.E., Danilenko V.N., Bekker O.B., Trenin A.S., Elizarov S.M., Dezhenkova L.G., Shtil A.A., Preobrazhenskaya M.N. // Journal of Antibiotics (Tokyo). 2012, №65 (8), P.405-411
  16. Simonova V.S., Samusenko A.V., Filippova N.A., Tevyashova A.N., Lyniv L.S., Kulik G.I., Chekhun V.F., Shtil A.A. // Bul. exp. biol. Med. 2005, V.4, P.451-455
  17. Shchekotikhin A.E., Glazunova V.A., Dezhenkova L.G., Shevtsova E.K., Traven’ V.F., Balzarini J., Huang H.-S., Shtil A.A., Preobrazhenskaya M.N. // European Journal of Medicinal Chemistry 2011, V.46, P.213-218
  18. Markova A.A., Plyavnik N.V., Pletneva M.V., Serebrennikova G.A., Shtil A.A. // Clin. Onkogematology. 2012, V.5, №2, P.141-143
  19. Gadalla AE., Pearson T., Currie AJ., Dale N., Hawley SA., Sheehan M., Hirst W., Michel AD., Randall A., Hardie DG., Frenguelli BG. // Journal of Neurochemistry. 2004, V.88, P.1272-1282

Views

Abstract - 232

PDF (English) - 102

PDF (Russian) - 58

Cited-By


PlumX

Dimensions

Refbacks

  • There are currently no refbacks.

Copyright (c) 2013 Glazunova V.A., Lobanov K.V., Shakulov R.S., Mironov A.S., Shtil A.A.

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies