The Hsp70 inhibiting peptide aptamer A17 potentiates radiosensitization of tumor cells by Hsp90 inhibition

Schilling D, Garrido C, Combs SE, Multhoff G (2017)

Publication Type: Journal article

Publication year: 2017

Journal

Cancer Letters Elsevier

Book Volume: 390

Pages Range: 146-152

DOI: 10.1016/j.canlet.2017.01.015

Abstract

The inhibition of heat shock protein 90 (Hsp90) is a promising strategy to increase the radiosensitivity of tumor cells. However, Hsp90 inhibition induces the expression of Hsp70 which is a prominent cytoprotective protein. Therefore, dual targeting of Hsp70 and Hsp90 might be beneficial to increase the radiosensitivity of tumor cells. Hsp70 inhibiting peptide aptamers have been shown to increase the sensitivity of tumor cells to apoptosis induced by different anticancer drugs. Herein, we studied the radiosensitizing activity of the Hsp70 inhibiting peptide aptamer A17 in combination with the Hsp90 inhibitor NVP-AUY922. Whereas A17 significantly increased apoptosis induction by NVP-AUY922 it did not significantly affect the radiosensitivity of human lung and breast cancer cells. However, Hsp70 inhibition by the aptamer A17 potentiated the radiosensitizing effects of the Hsp90 inhibitor NVP-AUY922. Mechanistically we speculate that an increased number of DNA double strand breaks and an enhanced G2/M arrest might be responsible for the increased radiosensitization in A17 expressing tumor cells. Therefore, the simultaneous inhibition of Hsp90 and Hsp70 combined with radiotherapy might provide a promising anti-cancer strategy.

Involved external institutions

Technische Universität München (TUM)

Germany (DE) National Institute for Health and Medical Research / Institut national de la santé et de la recherche médicale (INSERM)

France (FR)

How to cite

APA:

Schilling, D., Garrido, C., Combs, S.E., & Multhoff, G. (2017). The Hsp70 inhibiting peptide aptamer A17 potentiates radiosensitization of tumor cells by Hsp90 inhibition. Cancer Letters, 390, 146-152. https://doi.org/10.1016/j.canlet.2017.01.015

MLA:

Schilling, Daniela, et al. "The Hsp70 inhibiting peptide aptamer A17 potentiates radiosensitization of tumor cells by Hsp90 inhibition." Cancer Letters 390 (2017): 146-152.

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