The antitumor efficacy of the CK2 inhibitors so far described has not been extensively evaluated in cancer animal models. We have previously demonstrated that a proapoptotic cyclic peptide termed P15 delivered into the cells by the Tat Cell Penetrating Peptide was able to abrogate the CK2-mediated phosphorylation and induce tumor regression when injected directly into solid tumors in mice. Here we explored the antitumor effect by systemic administration of P15-Tat in a consecutive 5-day schedule through either intraperitoneal or intravenous route. Importantly, significant delay of tumor growth was observed at 2 mg/kg (p < 0.05), 10 mg/kg (p < 0.01) or 40 mg/kg (p < 0.001) after P15-Tat administration both in syngeneic murine tumors and human tumors xenografted in nude mice. In line with this, the systemic administration of P15-Tat induced apoptosis in the tumor as evidenced by in situ DNA fragmentation. Furthermore, we evidenced that 99mTc-labeled P15-Tat peptide was certainly accumulated on the tumors after administration by both routes. This report becomes the first describing the antitumor effect induced by systemic administration of a peptide that targets the acidic phosphorylation domain for CK2 substrates. Also, our data reinforces the perspectives of P15-Tat for the cancer targeted therapy.
Copyright 2007 Wiley-Liss, Inc.