A New Indole Derivative Decreased SALL4 Gene Expression in Acute Promyelocytic Leukemia Cell Line (NB4)

Authors
Zahra Sheikhrezaei 1
Parisa Heydari 1
Alireza Farsinezhad 1
Ahmad Fatemi 1
Soudeh Khanamani Falahati-Pour 2
Shokoofeh Darakhshan 3
Mojgan Noroozi Karimabad 4
Ali Darekordi 5
Hossein Khorramdelazad 4
Gholamhossein Hassanshahi 4
1 Department of Hematology and Medical Laboratory Sciences, Faculty of Allied Medical Sciences, Kerman University of Medical Sciences, Kerman, Iran
2 Pistachio Safety Research Center, Rafsanjan University of Medical Sciences, Rafsanjan, Iran
3 Department of Pediatrics, Rafsanjan University of Medical Sciences, Rafsanjan, Iran
4 Molecular Medicine Research Center, Rafsanjan University of Medical Sciences, Rafsanjan, Iran
5 Department of Chemistry, Faculty of Science, Vali-E-Asr University of Rafsanjan, Rafsanjan, Iran
10.22034/ibj.22.2.99
Abstract
Background: Acute myeloblastic leukemia (AML) is a clonal disorder due to bone marrow failure and uncontrolled proliferation of myeloid lineage. Acute promyelocytic leukemia (APL) is a subtype of AML. Heterocyclic compounds, such as indole, are considered as attractive candidates for cancer therapy, due to their abundance in nature and known biological activity. Sal-like protein (SALL4) is a zinc finger transcription factor involving in the multi-potency of stem cells, in the NB4 cell line. This study was aimed to evaluate the effects of basal indole and its new derivative, 2-(1-((2, 4-Aril)imino)-2,2,2-trifluoroethyl) phenyl-1H Indole-3- carbaldehyde (TFPHC), on the expression of SALL4. Methods: Cells were cultured and treated with different concentrations (75, 150, and 300 µg/mL) of the new indole derivative and DMSO, as a vehicle control, for 24 and 48 hours. Cell proliferation was evaluated by using Trypan blue exclusion and MTT assays. The percentage of apoptotic cells was determined by flowcytometry analysis using the Annexin V/PI apoptosis detection kit; mRNA expression of SALL4 was studied using absolute quantitative RT-PCR. Results: Our findings demonstrated the effects of new indole derivatives on SALL4 mRNA expression. Expression of SALL4 mRNA was significantly decreased at 75, 150, and 300 µg/mL concentrations. Conclusion: SALL4 plays a role in the survival of APL cells. SALL4 expression could be suppressed by the novel indole derivative. Additionally, SALL4 gene suppression can serve as a target in APL therapy.
Keywords
SALL4 protein
Indoles
Leukemia
Acute promyelocytic