Anti-Vascular Endothelial Growth Factor Targeting by Curcumin and Thalidomide in Acute Myeloid Leukemia Cells

Abstract

Acute myeloid leukemias (AMLs) are blood disorders that exhibit uncontrolled growth and reduction of apoptosis rates. As with other malignancies, progression may be result of induction and formation of new blood vessels influenced by disease conditions. Cancer cells produce a variety of factors which play important roles in angiogenesis. Vascular endothelial growth factor (VEGF) is critical for many malignancies, including AMLs. Curcumin, as a natural compound, is able to enhance apoptosis via a mechanism affecting regulatory genes. As a new strategy we here evaluated anti-VEGF properties of curcumin, alone and in combination with thalidomide, in leukemic cell lines. Growth inhibitory effects were assessed by MTT assay and apoptosis was detected by annexin/PI staining in U937 and KG-1 cell lines. mRNA expression levels of VEGF isoforms were evaluated by qRT-PCR. Curcumin inhibited proliferation and induced apoptosis in both KG-1 and U937 cells and this effect was stronger in combination with thalidomide. In KG-1 cells, the level of VEGF (A, B, C and D) mRNA was decreased in curcumin-treated as compared to untreated cells. Maximum effects were obtained at the concentration of 40 μM curcumin in U937 cells. Taken together, the results indicate that the VEGF autocrine loop may have an impact on AML development and progression and could be considered as a therapeutic target. Thalidomide as a VEGF inhibitor in combination with curcumin appears to have a synergistic impact on inhibition of cell proliferation and promotion of apoptosis.