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International Journal of Molecular Medicine
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October-2016 Volume 38 Issue 4

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Article

In vitro study comparing the efficacy of the water-soluble HSP90 inhibitors, 17-AEPGA and 17-DMAG, with that of the non‑water-soluble HSP90 inhibitor, 17-AAG, in breast cancer cell lines

  • Authors:
    • Tarik Ghadban
    • André Jessen
    • Matthias Reeh
    • Judith L. Dibbern
    • Sven Mahner
    • Volkmar Mueller
    • Ulrich F. Wellner
    • Cenap Güngör
    • Jakob R. Izbicki
    • Yogesh K. Vashist
  • View Affiliations / Copyright

    Affiliations: Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, D-20246 Hamburg, Germany, Gynecology Department and Clinic, University Medical Center Hamburg-Eppendorf, D-20246 Hamburg, Germany, Clinic for Surgery, University Clinic of Schleswig-Holstein, Campus Lübeck, D-23538 Lübeck, Germany
  • Pages: 1296-1302
    |
    Published online on: August 3, 2016
       https://doi.org/10.3892/ijmm.2016.2696
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Abstract

Heat shock protein (HSP)90 has emerged as an important target in cancer therapeutics. Diverse HSP90 inhibitors are under evaluation. The aim of the present study was to investigate the growth inhibitory effects of the newly developed water-soluble HSP90 inhibitors, 17-[2-(Pyrrolidin-1-yl)ethyl]amino-17-demethoxygeldanamycin (17-AEPGA) and 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG), compared to that of the non-water-soluble HSP90 inhibitor, 17-allylamino-17-demethoxygeldanamycin (17-AAG). The anti-proliferative effects of the 3 drugs on the human breast cancer cell lines, MCF-7, SKBR-3 and MDA-MB-231, were examined in vitro. In addition, tumor progression factors, including human epidermal growth factor receptor 2 (HER2), epidermal growth factor receptor 1 (EGFR1) and insulin-like growth factor type 1 receptor (IGF1R), as well as apoptotic markers were analysed. We found a time- and dose-dependent effect in all the tested cell lines. The effects of 17-AEPGA and 17-DMAG were equal or superior to those of 17-AAG. The 50% growth inhibition concentration was <2 µM for the water-soluble compounds following 72 h of exposure. The significant inhibition of HER2, EGFR1 and IGF1R protein expression was already evident at the concentration of 1 µM. Apoptosis was examined by caspase-3 and poly(ADP-ribose) polymerase (PARP) assay at the concentration of 1 µM of the inhibitors. HSP70 was upregulated, but HSP27 expression was not affected. Our data indicate that 17-AEPGA and 17-DMAG are highly active in breast cancer cell lines and may help to overcome the delivery issues associated with the use of 17-AAG.
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Copy and paste a formatted citation
Spandidos Publications style
Ghadban T, Jessen A, Reeh M, Dibbern JL, Mahner S, Mueller V, Wellner UF, Güngör C, Izbicki JR, Vashist YK, Vashist YK, et al: In vitro study comparing the efficacy of the water-soluble HSP90 inhibitors, 17-AEPGA and 17-DMAG, with that of the non‑water-soluble HSP90 inhibitor, 17-AAG, in breast cancer cell lines. Int J Mol Med 38: 1296-1302, 2016.
APA
Ghadban, T., Jessen, A., Reeh, M., Dibbern, J.L., Mahner, S., Mueller, V. ... Vashist, Y.K. (2016). In vitro study comparing the efficacy of the water-soluble HSP90 inhibitors, 17-AEPGA and 17-DMAG, with that of the non‑water-soluble HSP90 inhibitor, 17-AAG, in breast cancer cell lines. International Journal of Molecular Medicine, 38, 1296-1302. https://doi.org/10.3892/ijmm.2016.2696
MLA
Ghadban, T., Jessen, A., Reeh, M., Dibbern, J. L., Mahner, S., Mueller, V., Wellner, U. F., Güngör, C., Izbicki, J. R., Vashist, Y. K."In vitro study comparing the efficacy of the water-soluble HSP90 inhibitors, 17-AEPGA and 17-DMAG, with that of the non‑water-soluble HSP90 inhibitor, 17-AAG, in breast cancer cell lines". International Journal of Molecular Medicine 38.4 (2016): 1296-1302.
Chicago
Ghadban, T., Jessen, A., Reeh, M., Dibbern, J. L., Mahner, S., Mueller, V., Wellner, U. F., Güngör, C., Izbicki, J. R., Vashist, Y. K."In vitro study comparing the efficacy of the water-soluble HSP90 inhibitors, 17-AEPGA and 17-DMAG, with that of the non‑water-soluble HSP90 inhibitor, 17-AAG, in breast cancer cell lines". International Journal of Molecular Medicine 38, no. 4 (2016): 1296-1302. https://doi.org/10.3892/ijmm.2016.2696
Copy and paste a formatted citation
x
Spandidos Publications style
Ghadban T, Jessen A, Reeh M, Dibbern JL, Mahner S, Mueller V, Wellner UF, Güngör C, Izbicki JR, Vashist YK, Vashist YK, et al: In vitro study comparing the efficacy of the water-soluble HSP90 inhibitors, 17-AEPGA and 17-DMAG, with that of the non‑water-soluble HSP90 inhibitor, 17-AAG, in breast cancer cell lines. Int J Mol Med 38: 1296-1302, 2016.
APA
Ghadban, T., Jessen, A., Reeh, M., Dibbern, J.L., Mahner, S., Mueller, V. ... Vashist, Y.K. (2016). In vitro study comparing the efficacy of the water-soluble HSP90 inhibitors, 17-AEPGA and 17-DMAG, with that of the non‑water-soluble HSP90 inhibitor, 17-AAG, in breast cancer cell lines. International Journal of Molecular Medicine, 38, 1296-1302. https://doi.org/10.3892/ijmm.2016.2696
MLA
Ghadban, T., Jessen, A., Reeh, M., Dibbern, J. L., Mahner, S., Mueller, V., Wellner, U. F., Güngör, C., Izbicki, J. R., Vashist, Y. K."In vitro study comparing the efficacy of the water-soluble HSP90 inhibitors, 17-AEPGA and 17-DMAG, with that of the non‑water-soluble HSP90 inhibitor, 17-AAG, in breast cancer cell lines". International Journal of Molecular Medicine 38.4 (2016): 1296-1302.
Chicago
Ghadban, T., Jessen, A., Reeh, M., Dibbern, J. L., Mahner, S., Mueller, V., Wellner, U. F., Güngör, C., Izbicki, J. R., Vashist, Y. K."In vitro study comparing the efficacy of the water-soluble HSP90 inhibitors, 17-AEPGA and 17-DMAG, with that of the non‑water-soluble HSP90 inhibitor, 17-AAG, in breast cancer cell lines". International Journal of Molecular Medicine 38, no. 4 (2016): 1296-1302. https://doi.org/10.3892/ijmm.2016.2696
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