A therapeutic approach to treat prostate cancer by targeting Nm23-H1/h-Prune interaction(112 visite) Carotenuto M, de Antonellis P, Chiarolla CM, Attanasio C, Damiani V, Boffa I, Aiese N, Pedone E, Accordi B, Basso G, Navas L, Imbimbo C, Zollo M
Parole chiave: Competitive Permeable Peptide (cpp), H-Prune, Nm23-H1, Prostate Cancer,
*** IBB - CNR *** Centro di Ingegneria Genetica e Biotecnologia Avanzate (CEINGE), Naples, Italy. Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università di Napoli 'Federico II', Naples, Italy Istituto di Biostrutture e Bioimmagini, CNR, Naples, Italy Haemato-Oncology Laboratory, Department of Paediatrics, University of Padova, Padua, Italy Dipartimento di Neuroscienze e Scienze Riproduttive ed Odontostomatologiche, Università di Napoli 'Federico II', Naples, Italy DAI Dipartimento Assistenziale Medicina Trasfusionale, Azienda Ospedaliera Federico II, Naples, Italy
Nm23-H1 is a metastasis suppressor gene whose overexpression is associated with both reduced cell motility in various cancers and increased metastatic potential in neuroblastomas, osteosarcomas, and hematological malignances. We previously reported that Nm23-H1 exerts tumor suppressor action in prostate cancer cells and that h-Prune, which is overexpressed in various tumor types, binds Nm23-H1. Moreover, blockage of the Nm23-H1/h-Prune interaction with a competitive permeable peptide (CPP) attenuates migration of breast and neuroblastoma cells. This series of events suggests that the Nm23-H1/h-Prune protein complex regulates cancer progression and that its specific impairment could be a new therapeutic strategy in oncology. We found that CPP leads to inhibition of the AKT/mTORv and NF-kBv signaling pathways and also activates apoptosis. To obtain a proof-of-concept of our hypothesis, we used a xenograft model of prostate cancer to evaluate whether impairment of this complex using CPP results in an anti-tumoral effect. Using a mouse orthotopic model with bioluminescent imaging, we show evidences that CPP reduces prostate cancer metastases formation. In conclusion, CPP being able to impair formation of the h-Prune/Nm23-H1 complex holds promise for the treatment of prostate cancer.
17 Records (16 escludendo Abstract e Conferenze). Impact factor totale: 49.241 (46.833 escludendo Abstract e Conferenze). Impact factor a 5 anni totale: 51.033 (48.575 escludendo Abstract e Conferenze).