Author/Authors :
Sheikhrezaei, Zahra Department of Hematology and Medical Laboratory Sciences - Faculty of Allied Medical Sciences - Kerman University of Medical Sciences - Kerman, Iran , Heydari, Parisa Department of Hematology and Medical Laboratory Sciences - Faculty of Allied Medical Sciences - Kerman University of Medical Sciences - Kerman, Iran , Farsinezhad, Alireza Department of Hematology and Medical Laboratory Sciences - Faculty of Allied Medical Sciences - Kerman University of Medical Sciences - Kerman, Iran , Fatemi, Ahmad Department of Hematology and Medical Laboratory Sciences - Faculty of Allied Medical Sciences - Kerman University of Medical Sciences - Kerman, Iran , Falahati-Pour, Soudeh Khanamani Pistachio Safety Research Center - Rafsanjan University of Medical Sciences - Rafsanjan, Iran , Darakhshan, Shokoofeh Department of Pediatrics - Rafsanjan University of Medical Sciences - Rafsanjan, Iran , Noroozi Karimabad, Mojgan Molecular Medicine Research Center - Rafsanjan University of Medical Sciences - Rafsanjan, Iran , Khorramdelazad, Hossein Molecular Medicine Research Center - Rafsanjan University of Medical Sciences - Rafsanjan, Iran , Darekordi, Ali Rafsanjan University of Medical Sciences - Rafsanjan, Iran , Hassanshahi, Gholamhossein Department of Immunology- Rafsanjan University of Medical Sciences - Rafsanjan, Iran
Abstract :
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 :
Acute promyelocytic , Leukemia , Indoles , SALL4 protein