Arsenic Trioxide and Thalidomide Combination Induces Autophagy Along with Apoptosis in Acute Myeloid Cell Lines.

Author(s) Kian, M.Mohammadi; Haghi, A.; Salami, M.; Chahardouli, B.; Rostami, H.; Malekzadeh, K.; Foumani, H.Kamranzade; Mohammadi, S.; Nikbakht, M.
Journal Cell J
Date Published 2020 Jul

Objective: Autophagy and apoptosis play key roles in cancer survival and pathogenesis and are governed by specific genes which have a dual role in both cell death and survival. Arsenic trioxide (ATO) and thalidomide (THAL) are used for treatment of many types of hematologic malignancies. ATO prevents the proliferation of cells and induces apoptosis in some cancer cells. Moreover, THAL has immunomodulatory and antiangiogenic effects in malignant cells. The aim of present study was to examine the effects of ATO and THAL on U937 and KG-1 cells, and evaluation of mRNA expression level of VEGFs genes, PI3K genes and some of autophagy genes.

Materials and Methods: In this experimental study, U937 and KG-1 cells were treated by ATO (0.4-5 μM) and THAL (5-100 μM) for 24, 48 and 72 hours. Cell viability was measured by MTT assay. The apoptosis rate and cell cycle arrest were evaluated by flow cytometry (Annexin/PI) and cell cycle flow cytometry analysis, respectively. The effect of ATO/THAL on mRNAs expression was evaluated by real-time polymerase chain reaction (PCR).

Results: ATO/THAL combination enhanced cell apoptosis in a dose-dependent manner. Also, ATO/THAL induced SubG1/ G1 phase arrest. mRNA expression levels of (contrary to other isoform), and genes were upregulated in acute myeloid leukemia (AML) cells following treatment with ATO/THAL.

Conclusion: Combined treatment with ATO and THAL can inhibit proliferation and invasion of AML cells by down-regulating and and up-regulating and , and this effect was more marked than the effects of ATO and THAL alone.

DOI 10.22074/cellj.2020.6469
ISSN 2228-5806
Citation Cell J. 2020;22(2):193202.

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