Peptides and aptamers targeting HSP70: a novel approach for anticancer chemotherapy.
Fiche publication
Date publication
janvier 2011
Auteurs
Membres identifiés du Cancéropôle Est :
Dr GARRIDO Carmen, Dr GOBBO Jessica, Dr MICHEAU Olivier
Tous les auteurs :
Rerole AL, Gobbo J, De Thonel A, Schmitt E, Pais de Barros JP, Hammann A, Lanneau D, Fourmaux E, Deminov O, Micheau O, Lagrost L, Colas P, Kroemer G, Garrido C
Lien Pubmed
Résumé
The inhibition of heat shock protein 70 (HSP70) is an emerging strategy in cancer therapy. Unfortunately, no specific inhibitors are clinically available. By yeast two-hybrid screening, we have identified multiple peptide aptamers that bind HSP70. When expressed in human tumor cells, two among these peptide aptamers-A8 and A17-which bind to the peptide-binding and the ATP-binding domains of HSP70, respectively, specifically inhibited the chaperone activity, thereby increasing the cells' sensitivity to apoptosis induced by anticancer drugs. The 13-amino acid peptide from the variable region of A17 (called P17) retained the ability to specifically inhibit HSP70 and induced the regression of subcutaneous tumors in vivo after local or systemic injection. This antitumor effect was associated with an important recruitment of macrophages and T lymphocytes into the tumor bed. Altogether, these data indicate that peptide aptamers or peptides that target HSP70 may be considered as novel lead compounds for cancer therapy.
Référence
Cancer Res. 2011 Jan 15;71(2):484-95