Inhibitory Effects of Arsenic Trioxide and Thalidomide on Angiogenesis and Vascular Endothelial Growth Factor Expression in Leukemia Cells

Abstract

Acute myeloid leukemia (AML) is a blood disorder characterized by uncontrolled proliferation of myeloid<br />progenitors and decrease in the apoptosis rate. The vascular endothelial growth factor (VEGF) promotes blood vessel<br />regeneration which might play important roles in development and progression of neoplasia. Our previous studies<br />focused on cytotoxicity and anticancer effects of arsenic trioxide (ATO) and thalidomide (THAL) as an anti-VEGF<br />compound in the AML cell model. ATO also affects regulatory genes involved in cell proliferation and apoptosis. The<br />aim of present study was to examine the effects of ATO and THAL alone and in combination on U937 and KG-1 cells<br />, with attention to mRNA expression for VEGF isoforms. Growth inhibitory effects was assessed by MTT assay and<br />apoptosis induction was determined by Annexin/PI staining. mRNA expression levels were evaluated by real-time<br />PCR. Our data indicated that ATO (1.618μM and 1μM in KG-1 and U937 cell lines respectively), THAL (80μM and<br />60μM) and their combination inhibited proliferation and induced apoptosis in our cell lines. mRNA expression of<br />VEGF (A, B) decreased while C and D isoforms did not show any significant changes. Taken together, according to<br />the obtained results, the VEGF autocrine loop could be a target as a therapeutic strategy for cases of AML.