Open Access

Potent antitumor activity of the novel HSP90 inhibitors AUY922 and HSP990 in neuroendocrine carcinoid cells

  • Authors:
    • Kathrin Zitzmann
    • Galina Ailer
    • George Vlotides
    • Gerald Spoettl
    • Julian Maurer
    • Burkhard Göke
    • Felix Beuschlein
    • Christoph J. Auernhammer
  • View Affiliations

  • Published online on: October 4, 2013     https://doi.org/10.3892/ijo.2013.2130
  • Pages: 1824-1832
  • Copyright: © Zitzmann et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

The heat shock protein (HSP) 90 chaperone machine involved in numerous oncogenic signaling pathways is overexpressed in cancer cells and is currently being evaluated for anticancer therapy. Neuroendocrine tumors (NETs) of the gastroenteropancreatic (GEP) system comprise a heterogeneous group of tumors with increasing incidence and poor prognosis. Here, we report the antiproliferative effects of the HSP90 inhibitors AUY922 and HSP990 in neuroendocrine tumor cells. Treatment of human pancreatic BON1, bronchopulmonary NCI-H727 and midgut carcinoid GOT1 neuroendocrine tumor cells with increasing concentrations of AUY922 and HSP990 dose-dependently suppressed cell viability. Significant effects on neuroendocrine cell viability were observed with inhibitor concentrations as low as 5 nM. Inhibition of cell viability was associated with the induction of apoptosis as demonstrated by an increase in sub-G1 events and PARP cleavage. HSP90 inhibition was associated with decreased neuroendocrine ErbB and IGF-I receptor expression, decreased Erk and Akt phospho­rylation and the induction of HSP70 expression. These findings provide evidence that targeted inhibition of upregulated HSP90 activity could be useful for the treatment of aggressive neuroendocrine tumors resistant to conventional therapy.
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December 2013
Volume 43 Issue 6

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

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APA
Zitzmann, K., Ailer, G., Vlotides, G., Spoettl, G., Maurer, J., Göke, B. ... Auernhammer, C.J. (2013). Potent antitumor activity of the novel HSP90 inhibitors AUY922 and HSP990 in neuroendocrine carcinoid cells. International Journal of Oncology, 43, 1824-1832. https://doi.org/10.3892/ijo.2013.2130
MLA
Zitzmann, K., Ailer, G., Vlotides, G., Spoettl, G., Maurer, J., Göke, B., Beuschlein, F., Auernhammer, C. J."Potent antitumor activity of the novel HSP90 inhibitors AUY922 and HSP990 in neuroendocrine carcinoid cells". International Journal of Oncology 43.6 (2013): 1824-1832.
Chicago
Zitzmann, K., Ailer, G., Vlotides, G., Spoettl, G., Maurer, J., Göke, B., Beuschlein, F., Auernhammer, C. J."Potent antitumor activity of the novel HSP90 inhibitors AUY922 and HSP990 in neuroendocrine carcinoid cells". International Journal of Oncology 43, no. 6 (2013): 1824-1832. https://doi.org/10.3892/ijo.2013.2130