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

Mohammadi Kian, Mahnaz; Mohammadi, Saeed; Tavallaei, Mahmoud; Chahardouli, Bahram; Rostami, Saharbano; Zahedpanah, Mahdi; Ghavamzadeh, Ardeshir; Nikbakht, Mohsen

doi:10.22034/APJCP.2018.19.4.1127

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

Document Type : Research Articles

Authors

¹ Hematology Oncology and Stem Cell Transplantation Research Center, Tehran University of Medical Sciences, Tehran, Iran.

² Hematologic Malignancies Research Center, Tehran University of Medical Sciences, Tehran, Iran.

³ Human Genetics Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran.

⁴ Department of Medical Laboratory Sciences, Faculty of Allied Medicine, Qazvin University of Medical Sciences, Qazvin, Iran.

10.22034/APJCP.2018.19.4.1127

Abstract

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

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