CIGB-300, a proapoptotic peptide, inhibits angiogenesis in vitro and in vivo.

FARINA HG; BENAVENT ACERO F1; PERERA Y; RODRÍGUEZ A; PEREA S2, ACEVEDO CASTRO ; ROBERTO GOMEZ, DANIEL F. ALONSO, AND DANIEL E. GOMEZ

Varadero

Congreso; Second International Congress on Immunopharmacology IMMUNOPHARMACOLOGY 2011; 2011

Cuban Society of Pharmacology

We have previously demonstrated that a proapoptotic cyclic peptide CIGB-300, formerly known as P15-tat delivered into the cells by the Cell Penetrating Peptide Tat was able to abrogate the CK2-mediated phosphorylation and induce tumor regression when injected directly into solid tumors in mice or by systemic administration. In this work, we studied the role of CIGB-300 on the main events that take place in angiogenesis. At non cytotoxic doses, CIGB-300 was able to inhibit adhesion, migration and tubular network formation induced by human umbilical vein endothelial cells (HUVEC) growing upon Matrigel in vitro. Likewise, we evaluated the cellular penetration and localization into the HUVEC cells of CIGB-300. Our results confirmed a quick cellular penetration and a cytoplasmic accumulation in the early minutes of incubation and a translocation into the nuclei beginning at 12 hours of treatment, with a strong presence in the perinuclear area. A microarray analyses was used to determine the genes affected by the treatment. We observed that CIGB-300 significantly decreased four genes strongly associated with tubulogenesis, growth and differentiation of endothelial cells. The CIGB-300 was tested in vivo on chicken embryo chorioallantoic membranes (CAM), and a large number of newly formed blood vessels were significantly regressed. The results suggested that CIGB-300 has potential as an antiangiogenic treatment. The mechanism of action may be associated with partial inhibition of VEGF and Notch pathways.