close
Skip to main content
Springer Nature Link
Log in

Telomerase inhibitors as novel antitumor drugs

  • Published:
Save article
View saved research
BERJAYA Applied Biochemistry and Microbiology Aims and scope Submit manuscript

Abstract

Telomerase activity is detected in most types of human tumors, but it is almost undetectable in normal somatic cells; therefore, telomerase is a promising therapeutic target. The present review describes various approaches to telomerase inhibition, namely, antisense therapy, RNA interference, and the use of ribozymes and agents interacting with the telomeric G-quadruplex. The use of these compounds in clinical research is analyzed in the review.

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

Access this article

Log in via an institution

Subscribe and save

Springer+
from $39.99 /Month
  • Starting from 10 chapters or articles per month
  • Access and download chapters and articles from more than 300k books and 2,500 journals
  • Cancel anytime
View plans

Buy Now

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

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Explore related subjects

Discover the latest articles, books and news in related subjects, suggested using machine learning.

Abbreviations

2-5A:

2′,5′-tetraadenylate

AZT:

azidothymidine (3′-azido-2′,3′-dideoxythymidine)

ddG:

dideoxyguanosine

ddGTP:

dideoxyguanosine triphosphate

dsRNA:

double stranded RNA

EGCG:

epigallocatechin gallate

IC50 :

inhibitor concentration at which the TA decreases twofold

hTERT:

the catalytic subunit of human telomerase

hTR:

the RNA component of human telomerase

GRN163:

N3′-P5′-thiophosphoramidate (13-nucleotide)

NP:

oligonucleotides-phosphoramidate oligonucleotides

NPS:

oligonucleotides-N3′-P5′-thiophosphoramidates

ODN:

DNA oligonucleotides

ORN:

RNA oligonucleotides

PNA:

peptidonucleic acids

PS:

phosphorothioate

RISC:

RNA-protein complexes

siRNA:

small interfering RNAs

TA:

telomerase activity

TMO (telomere mimic oligonucleotides):

oligonucleotides consisting of telomeric repeats

TMPyP4:

tetra-(N-methyl-4-pyridyl)-porphine

TRAP:

telomerase activity assay procedure

References

  1. Kim, N.W., Piatyszek, M.A., Prowse, K.R., Harley, C.B., West, M.D., Ho, P.L., Covielio, G.M., Wright, W.E., Weinrich, S.L., and Shay, J.W., Science, 1994, vol. 266, pp. 2011–2015.

    Article  PubMed  CAS  Google Scholar 

  2. Shay, J.W. and Wright, W.E., Curr. Opin. Oncol., 1996, vol. 8, pp. 66–71.

    Article  PubMed  CAS  Google Scholar 

  3. Masutomi, K., Yu, E.Y., Khurts, S., Ben-Porath, I., Currier, J.L., Metz, G.V., Brooks, M.W., Kaneko, S., Murakami, S., DeCaprio, J.A., Weinberg, R.A., Stewart, S.A., and Hahn, W.C., Cell, 2003, vol. 114, no. 2, pp. 241–253.

    Article  PubMed  CAS  Google Scholar 

  4. Blackburn, E.H., FEBS Lett., 2005, vol. 579, no. 4, pp. 859–862.

    Article  PubMed  CAS  Google Scholar 

  5. Feng, J., Funk, W.D., Wang, S.S., Weinrich, S.L., Avilion, A.A., Chiu, C.P., Adams, R.R., Chang, E., Allsopp, R.C., and Yu, J., Science, 1995, vol. 269, pp. 1236–1241.

    Article  PubMed  CAS  Google Scholar 

  6. Blackburn, E.H. and Gall, J.G., J. Mol. Biol., 1978, vol. 120, pp. 33–63.

    Article  PubMed  CAS  Google Scholar 

  7. Wick, M., Zubov, D., and Hagen, G., Gene, 1999, vol. 232, pp. 97–106.

    Article  PubMed  CAS  Google Scholar 

  8. Cong, Y.S., Wen, J., and Bacchetti, S., Hum. Mol. Genet., 1999, vol. 8, pp. 137–142.

    Article  PubMed  CAS  Google Scholar 

  9. Bodnar, A.G., Ouellette, M., Frolkis, M., Holt, S.E., Chiu, C.P., Morin, G.B., Harley, C.B., Shay, J.W., Lichtsteiner, S., and Wright, W.E., Science, 1998, vol. 279, pp. 349–352.

    Article  PubMed  CAS  Google Scholar 

  10. Glukhov, A.I., Gordeev, S.A., Apryatin, S.A., and Severin, S.E., Vestn. Nauch.-Issled. Inst. Mol. Med., 2006, vol. 6, pp. 33–56

    Google Scholar 

  11. Gomez, D.E., Tejera, A.M., and Olivero, O.A., Biochem. Biophys. Res. Commun., 1998, vol. 246, no. 1, pp. 107–110.

    Article  PubMed  CAS  Google Scholar 

  12. Pai, R.B., Pai, S.B., Kukhanova, M., Dutschman, G.E., Guo, X., and Cheng, Y., Cancer Res., 1998, vol. 58, pp. 1909–1913.

    PubMed  CAS  Google Scholar 

  13. Strahl, C. and Blackburn, E.H., Mol. Cell. Biol., 1996, vol. 16, pp. 53–65.

    PubMed  CAS  Google Scholar 

  14. De Cian, A., Lacroix, L., Douarre, C., TemimeSmaali, N., Trentesaux, C., Riou, J.F., and Mergny, J.L., Biochimie, 2008, vol. 90, pp. 131–155.

    Article  PubMed  Google Scholar 

  15. Pendino, F., Flexor, M., Delhommeau, F., Buet, D., Lanotte, M., and Segal-Bendirdjian, E., Proc. Natl. Acad. Sci., 2001, vol. 98, no. 12, pp. 6662–6667.

    Article  PubMed  CAS  Google Scholar 

  16. Togashi, K., Kakeya, H., Morishita, M., Song, Y., and Osada, H., Oncol. Res., 1998, vol. 10, pp. 449–453.

    PubMed  CAS  Google Scholar 

  17. Yamakuchi, M., Nakata, M., Kawahara, K., Kitajima, I., and Maruyama, I., Cancer Lett., 1997, vol. 119, no. 2, pp. 213–219.

    Article  PubMed  CAS  Google Scholar 

  18. Huang, P.R., Yeh, Y.M., and Wang, T.C., Cancer Lett., 2005, vol. 227, no. 2, pp. 169–174.

    Article  PubMed  CAS  Google Scholar 

  19. Naasani, I., Seimiya, H., and Tsuruo, T., Biochem. Biophys. Res. Commun. 1998, vol. 249, pp. 391–396.

    Article  PubMed  CAS  Google Scholar 

  20. Eder, P.S., DeVine, R.J., Dagle, J.M., and Walder, J.A., Antisense Res. Dev., 1991, vol. 1, pp. 141–151.

    PubMed  CAS  Google Scholar 

  21. Feng, J., Funk, W.D., Wang, S., Weinrich, S.L., Avilion, A.A., Chiu, C., Adams, R.R., Chang, E., Allsopp, R.C., Yu, J.H., Le, S.Y., West, M.D., Harley, C.B., Andrews, W.H., Greider, C.W., and Vifleponteau, B., Science, 1995, vol. 269, pp. 1236–1241.

    Article  PubMed  CAS  Google Scholar 

  22. Glukhov, A.I., Zimnik, O.V., Gordeev, S.A., and Severin, S.E., Biochem. Biophys. Res. Commun., 1998, vol. 248, pp. 368–371.

    Article  PubMed  CAS  Google Scholar 

  23. Norton, J.C., Piatyszek, M.A., Wright, W.E., Shay, J.W., and Corey, D.R., Nature Biotechnol., 1996, vol. 14, pp. 615–619.

    Article  CAS  Google Scholar 

  24. Hamilton, S.E., Pitts, A.E., Katipally, R.R., Jia, X., Davies, B.A., Rulter, J.P., Wright, W.R., Shay, J.W., and Corey, D.R., Biochemistry, 1997, vol. 36, pp. 11873–11880.

    Article  PubMed  CAS  Google Scholar 

  25. Gryaznov, S., Asai, A., Oshima, Y., Yamamoto, Y., Pongracz, K., Pruzan, R., Wunder, E., Piatyszek, M., Li, S., Chin, A., Harley, Ñ., Akinaga, S., and Yamashita, Y., Nucleosides Nucleotides Nucleic Acids, 2003, vol. 22, pp. 577–581.

    Article  PubMed  CAS  Google Scholar 

  26. Wang, E.S., Wu, K., Chin, A.C., Chen-Kiang, S., Pongracz, K., Gryaznov, S., and Moore, M.A., Blood, 2004, vol. 103, no.1, pp. 258–266.

    Article  Google Scholar 

  27. Djojosubroto, M.W., Chin, A.C., Go, N., Schaetzlein, S., Manns, M.P., Gryaznov, S., Harley, C.B., and Rudolph, K.L., Hepatology, 2005, vol. 42, no. 5, pp. 1127–1136.

    Article  PubMed  CAS  Google Scholar 

  28. Herbert, B.S., Gellert, G.C., Hochreiter, A., Pongracz, K., Wright, W.E., Zielinska, D., Chin, A.C., Harley, C.B., Shay, J.W., and Gryaznov, S.M., Oncogene, 2005, vol. 24, no. 33, pp. 5262–5268.

    Article  PubMed  CAS  Google Scholar 

  29. Kondo, S., Kondo, Y., Li, G., Silverman, R.H., and Cowell, J.K., Oncogene, 1998, vol. 16, no. 25, pp. 3323–3330.

    Article  PubMed  CAS  Google Scholar 

  30. Kondo, Y., Kondo, Y., Koga, S., Komata, T., and Kondo, S., Oncogene, 2000, vol. 19, no. 18, pp. 2205–2211.

    Article  PubMed  CAS  Google Scholar 

  31. Kraemer, K., Fuessel, S., Schmidt, U., Kotzsch, M., Schwenzer, B., Wirth, M.P., and Meye, A., Clin. Cancer Res., 2003, vol. 9, no. 10, pp. 3794–3800.

    PubMed  CAS  Google Scholar 

  32. Cao, Y., Li, H., Deb, S., and Liu, J.P., Oncogene, 2002, vol. 21, no. 20, pp. 3130–3138.

    Article  PubMed  CAS  Google Scholar 

  33. Kanazawa, Y., Ohkawa, K., Ueda, K., Mita, E., Takehara, T., Sasaki, Y., Kasahara, A., and Hayashi, N., Biochem. Biophys. Res. Commun., 1996, vol. 225, no. 2, pp. 570–576.

    Article  PubMed  CAS  Google Scholar 

  34. Yeo, M., Rha, S.Y., Jeung, H.C., Hu, S.X., Yang, S.H., Kim, Y.S., An, S.W., and Chung, H.C., Int. J. Cancer, 2005, vol. 114, no. 3, pp. 484–489.

    Article  PubMed  CAS  Google Scholar 

  35. Wan, M.S.K., Fell, P.L., and Akhtar, S., Antisense Nucleic Acid Drug Devel., 1998, vol. 8, pp. 309–317.

    Article  CAS  Google Scholar 

  36. Yokoyama, Y., Takahashi, Y., Shinohara, A., Wan, X., Taka-hashi, S., Niwa, K., and Tamaya, T., Biochem. Biophys. Res. Commun., 2000, vol. 273, no. 1, pp. 316–321.

    Article  PubMed  CAS  Google Scholar 

  37. Ludwig, A., Saretzki, G., Holm, P.S., Tiemann, F., Lorenz, M., Emrich, T., Harley, C.B., and von Zglinicki, T., Cancer Res., 2001, vol. 61, no. 7, pp. 3053–3061.

    PubMed  CAS  Google Scholar 

  38. Zahler, A.M., Williamson, J.R., Cech, T.R., and Prescott, D.M., Nature, 1991, vol. 350, pp. 718–720.

    Article  PubMed  CAS  Google Scholar 

  39. Phatak, P. and Burger, A.M., Br. J. Pharmacol., 2007, vol. 152, pp. 1003–1011.

    Article  PubMed  CAS  Google Scholar 

  40. Sun, D., Thompson, B., and Cathers, B.E., J. Med. Chem., 1997, vol. 40, pp. 2113–2116.

    Article  PubMed  CAS  Google Scholar 

  41. Perry, P.J., Gowan, S.M., Reszka, A.P., Polucci, P., Jenkins, T.C., Kelland, L.R., and Neidle, S., J. Med. Chem., 1998, vol. 41, pp. 3253–3260.

    Article  PubMed  CAS  Google Scholar 

  42. Cairns, D., Michalitsi, E., Jenkins, T., and Mackay, S., Bioorg. Med. Chem., 2002, vol. 10, no. 3, pp. 803–807.

    Article  PubMed  CAS  Google Scholar 

  43. Wheelhouse, R.T., Sun, D., Han, H., Han, F.X., and Hurley, L.H., J. Amer. Chem. Soc., 1998, vol. 120, pp. 3261–3262.

    Article  CAS  Google Scholar 

  44. Siddiqui-Jain, A., Grand, C.L., Bearss, D.J., and Hurley, L., Proc. Natl. Acad. Sci. USA, 2002, vol. 99, no. 18, pp. 11593–11598.

    Article  PubMed  CAS  Google Scholar 

  45. Binz, N., Shalaby, T., Rivera, P., Shinyab, K., and Grotzer, M.A., Eur. J. Cancer, 2005, vol. 41, no. 18, pp. 2873–2881.

    Article  PubMed  CAS  Google Scholar 

  46. Sissi, C., Lucatello, L., Paul Krapcho, A., Maloney, D.J., Boxer, M.B., Camarasa, M.V., Pezzoni, G., Menta, E., and Palumbo, M., Bioorg. Med. Chem., 2007, vol. 15, no. 1, pp. 555–562.

    Article  PubMed  CAS  Google Scholar 

  47. Fire, A., Xu, S., Montgomery, M.K., Kostas, S.A., Driver, S.E., and Mello, C.C., Nature, 1998, vol. 391, pp. 806–811.

    Article  PubMed  CAS  Google Scholar 

  48. Kosciolek, B.A., Kalanlidis, K., Tabler, M., and Rowley, P.T., Mol. Cancer Ther., 2003, vol. 2, no. 3, pp. 209–216.

    PubMed  CAS  Google Scholar 

  49. Shammas, M.A., Koley, H., Batchu, R.B., Bertheau, R.C., Protopopov, A., Munshi, N.C., and Goyal, R.K., Mol. Cancer, 2005, vol. 4, pp. 24–25.

    Article  PubMed  Google Scholar 

  50. Li, S., Crothers, J., Haqq, C.M., and Blackburn, E.H., J. Biol. Chem., 2005, vol. 280, no. 25, pp. 23709–23717.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Sechenov Medical Academy, Moscow, 119435, Russia

    A. I. Glukhov & S. E. Severin

  2. Moscow Research Institute of Medical Ecology, Moscow, 117149, Russia

    A. I. Glukhov, L. V. Svinareva & S. E. Severin

  3. Lomonosov Moscow State Academy of Fine Chemical Technology, Moscow, 119571, Russia

    L. V. Svinareva & V. I. Shvets

Authors
  1. A. I. Glukhov
    View author publications

    Search author on:PubMed Google Scholar

  2. L. V. Svinareva
    View author publications

    Search author on:PubMed Google Scholar

  3. S. E. Severin
    View author publications

    Search author on:PubMed Google Scholar

  4. V. I. Shvets
    View author publications

    Search author on:PubMed Google Scholar

Corresponding author

Correspondence to L. V. Svinareva.

Additional information

Original Russian Text © A.I. Glukhov, L. V. Svinareva, S.E. Severin, V.I. Shvets, 2010, published in Biotekhnologiya, 2010, No. 4, pp. 8–16.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Glukhov, A.I., Svinareva, L.V., Severin, S.E. et al. Telomerase inhibitors as novel antitumor drugs. Appl Biochem Microbiol 47, 655–660 (2011). https://doi.org/10.1134/S0003683811070039

Download citation

  • Received:

  • Published:

  • Issue date:

  • DOI: https://doi.org/10.1134/S0003683811070039

Keywords