Peptide Aptamers targeting mutant p53 induce apoptosis in tumor cells

GUIDA E.; BISSO A.; FENOLLAR-FERRER C.; NAPOLI M.; ANSELMI C.; GIRARDINI J.E.; CARLONI P.; DEL SAL G.

CANCER RESEARCH

Año: 2008 vol. 68 p. 6550 - 6558

0008-5472

Mutations in the p53 tumor suppressor gene frequently resultin expression of p53 point mutants that accumulate in cancercells and actively collaborate with tumor progression throughthe acquisition of novel properties. Interfering with mutantp53 functions may represent a valid alternative for blockingtumor growth and development of aggressive phenotypes. Theinteractions and activities of selected proteins can bespecifically modulated by the binding of peptide aptamers(PA). In the present work, we isolated PAs able to interactmore efficiently with p53 conformational mutants comparedwith wild-type p53. The interaction between mutant p53 andPAs was further characterized using molecular modeling.Transient expression of PAs was able to reduce the transactivationactivity of mutant p53 and to induce apoptosisspecifically in cells expressing mutant p53. These PAs couldprovide a potential strategy to inhibit the oncogenic functionsof mutant p53 and improve mutant p53-targeted cancertherapies.