FEBS Letters
FEBS Letters
5 years ago

Peptide fragments of Hsp70 modulate its chaperone activity and sensitize tumor cells to anti-cancer drugs

Dmitry V. Sverchinsky, Vladimir A. Mitkevich, Pavel I. Semenyuk, Irina V. Guzhova, Boris A. Margulis, Vladimir F. Lazarev
Most Hsp70 chaperone inhibitors exert anti-cancer effects; however, their high cytotoxicity prompted us here to employ peptide fragments of the chaperone as safer modulators of its activity and as complements to customary drugs. One such peptide, ICit-2, was found to inhibit substrate-binding and refolding activities of the chaperone. Using various approaches, we established that ICit-2 binds Hsp70, which may explain its inhibitory action. ICit-2 penetrates A-431 cancer cells and, in combination with doxorubicin, enhances the cytotoxicity and growth inhibitory effect of the drug. Similarly, using the B16 mouse melanoma model, we found that ICit-2 inhibits the rate of tumor growth by 48% compared with doxorubicin alone, proving that the peptide can be employed to sensitize resistant tumors to cytostatic medicines. This article is protected by copyright. All rights reserved.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1002/1873-3468.12913

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