The Hsp70 inhibiting peptide aptamer A17 potentiates radiosensitization of tumor cells by Hsp90 inhibition. (1st April 2017)

• Record Type: Journal Article
• Authors: Schilling, Daniela; Garrido, Carmen; Combs, Stephanie E.; Multhoff, Gabriele
• Is Part Of: Cancer letters. Volume 390(2017)
• Page Start: 146
• Page End: 152
• Publication Date: 2017-04-01
• Subjects: Heat shock protein 70 (Hsp70) -- Heat shock protein 90 (Hsp90) -- Radiosensitization -- NVP-AUY922 -- Aptamer; Hsp heat shock protein -- HSF1 heat shock factor 1 -- SER sensitizing enhancement ratio; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Electronic journals; 616.994
• DOI: 10.1016/j.canlet.2017.01.015
• Languages: English
• ISSNs: 0304-3835

Abstract

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. Highlights: Hsp70 inhibiting peptide aptamer A17 sensitizes cancer cells to Hsp90 inhibition. A17 potentiates radiosensitization by Hsp90 inhibition. A17 enhances DNA double strand breaks and G2 /M cell cycle arrest.