AKT/NF-kappaB inhibitor xanthohumol targets cell growth and angiogenesis in hematologic malignancies.

BACKGROUND

Leukemias are dependent on Akt/NF-kappaB activation and angiogenesis.

METHODS

The antiangiogenic Akt/NF-kappaB inhibitor xanthohumol (XN) has in vitro activity against acute and chronic myelogenous leukemia cell lines (AML, CML) and fresh samples from patients were investigated.

RESULTS

Inhibition of cell proliferation is associated with induction of apoptosis and reduced VEGF secretion. Decreased cell invasion, metalloprotease production, and adhesion to endothelial cells observed in the presence of XN could prevent in vivo life-threatening complications of leukostasis and tissue infiltration.

CONCLUSIONS

As endothelial cells and hematopoietic cells are mutually correlated in their development and growth, targeting both tumor cells and endothelial cells with agents possessing cytotoxic and antiangiogenic activities may lead to synergistic antitumor effects interrupting a reciprocal stimulatory loop between leukemia and endothelial cells.