title: Peptides and aptamers targeting HSP70: a novel approach for anticancer chemotherapy.
abstract: 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.
authors.affiliation: INSERM UMR 866, Faculty of Medicine and Pharmacy, Dijon, France.
authors.forename: Anne-Laure
authors.initials: AL
authors.lastname: Rérole
authors.forename: Jessica
authors.initials: J
authors.lastname: Gobbo
authors.forename: Aurelie
authors.initials: A
authors.lastname: De Thonel
authors.forename: Elise
authors.initials: E
authors.lastname: Schmitt
authors.forename: Jean Paul
authors.initials: JP
authors.lastname: Pais de Barros
authors.forename: Arlette
authors.initials: A
authors.lastname: Hammann
authors.forename: David
authors.initials: D
authors.lastname: Lanneau
authors.forename: Eric
authors.initials: E
authors.lastname: Fourmaux
authors.forename: Oleg N
authors.initials: ON
authors.lastname: Demidov
authors.forename: Oleg
authors.initials: O
authors.lastname: Deminov
authors.forename: Olivier
authors.initials: O
authors.lastname: Micheau
authors.forename: Laurent
authors.initials: L
authors.lastname: Lagrost
authors.forename: Pierre
authors.initials: P
authors.lastname: Colas
authors.forename: Guido
authors.initials: G
authors.lastname: Kroemer
authors.forename: Carmen
authors.initials: C
authors.lastname: Garrido
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D052158:Aptamers, Peptide / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology*; D018840:HSP70 Heat-Shock Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008546:Melanoma, Experimental / Q000188:drug therapy; D051379:Mice; D008810:Mice, Inbred C57BL; D058990:Molecular Targeted Therapy / Q000379:methods*; D010455:Peptides / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology*; D017434:Protein Structure, Tertiary; D051381:Rats; D014162:Transfection
chemical_list: D000970:Antineoplastic Agents; D052158:Aptamers, Peptide; D018840:HSP70 Heat-Shock Proteins; D010455:Peptides