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

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.