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

Abstract

Most Hsp70 chaperone inhibitors exert anti-cancer effects; however, their high cytotoxicity proposed the use of 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 (Dox), 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 to Dox alone, confirming that the peptide can be employed to sensitize resistant tumors to cytostatic medicines.