Selectivity analysis of protein kinase CK2 inhibitors DMAT, TBB and resorufin in cisplatin-induced stress responses

  • Authors:
    • Gerhard Fritz
    • Olaf-Georg Issinger
    • Birgitte Brinkmann Olsen
  • View Affiliations

  • Published online on: November 1, 2009     https://doi.org/10.3892/ijo_00000431
  • Pages: 1151-1157
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Abstract

Targeting protein kinases as a therapeutic approach to treat various diseases, especially cancer is currently a fast growing business. Although many inhibitors are available, exhibiting remarkable potency, the major challenge is their selectivity. Here we show that the protein kinase CK2 inhibitors DMAT, TBB and resorufin differ in their selectivity against PI3K family members, since PI3K and DNA-PK are subject to inhibition by DMAT and TBB, however, not by resorufin. TBB and DMAT treatment together with cisplatin lead to an inhibition of cisplatin-induced stress signaling (as detected by phosphorylation of JNK and H2AX). In the case of resorufin no interference with the stress-signaling pathway is observed, supporting the notion that TBB and DMAT interfere with upstream molecules involved in genotoxic stress signaling. We have also tested the protein kinase CK2 inhibitors with respect to cell viability and inhibition of endogenous CK2 activity in the absence and presence of the anti-cancer drug cisplatin. The strongest effect on viability was observed with resorufin. In contrast to resorufin, TBB protected cells from cisplatin-induced cell killing. Furthermore, the inhibition of endogenous CK2 activity was cell type-dependent as endogenous CK2 was inhibited to different degrees in the cell lines.

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November 2009
Volume 35 Issue 5

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Fritz G, Issinger O and Olsen BB: Selectivity analysis of protein kinase CK2 inhibitors DMAT, TBB and resorufin in cisplatin-induced stress responses. Int J Oncol 35: 1151-1157, 2009
APA
Fritz, G., Issinger, O., & Olsen, B.B. (2009). Selectivity analysis of protein kinase CK2 inhibitors DMAT, TBB and resorufin in cisplatin-induced stress responses. International Journal of Oncology, 35, 1151-1157. https://doi.org/10.3892/ijo_00000431
MLA
Fritz, G., Issinger, O., Olsen, B. B."Selectivity analysis of protein kinase CK2 inhibitors DMAT, TBB and resorufin in cisplatin-induced stress responses". International Journal of Oncology 35.5 (2009): 1151-1157.
Chicago
Fritz, G., Issinger, O., Olsen, B. B."Selectivity analysis of protein kinase CK2 inhibitors DMAT, TBB and resorufin in cisplatin-induced stress responses". International Journal of Oncology 35, no. 5 (2009): 1151-1157. https://doi.org/10.3892/ijo_00000431