Amifostine exerts anti-angiogenic activity and suppresses vascular endothelial growth factor secreted by hemopoietic stem/progenitor cells

ABSTRACT

To assess, in vitro, the effect of Amifostine [AMF, WR-2721] on angiogenesis and levels of vascular endothelial growth factor [VEGF] secreted from hemopoietic stem/progenitor cell populations. We conducted the study in the research laboratories of the Hashemite University, Jordan between September 2003 and January 2005 where we took samples were from Myelodysplastic syndrome [MDS] patients and healthy donors attending Al-Hussein Cancer Center and We determined the proliferation of human umbilical vein endothelial cells [HUVECs] in cultures supplemented with media conditioned with AMF-treated and AMF-untreated pure hemopoietic cells [CD34+ cells, and erythroid, myeloid and megakaryocytic progenitors]. Furthermore, in the same conditioned media, we evaluated levels of elaborated VEGF by a sensitive enzyme linked immunosorbent assay. Biologically, media conditioned with AMF-treated cells reduced proliferation of HUVECs compared to media conditioned with untreated control cells [p<0.05]. In cultures of AMF-untreated cells, elaboration of VEGF was higher [p<0.05] in media conditioned with cells from MDS patients compared to healthy donors. A 30 minutes pre-exposure of cells to AMF [500 mM] suppressed levels of VEGF secreted within 24 hours in 63 of 89 evaluated cultures. The percentage of reduction of VEGF in AMF-sensitive cultures was comparable in cultures of MDS cells [18%, 2-37%; median, range] and normal cells [12%, 2-45%]. The results showed that AMF exerts an anti-angiogenic activity and suppresses the secretion of VEGF in hemopoietic stem/progenitor cells obtained from both healthy individuals and patients with MDS