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Apoptosis-Inducing Effect of Spiroaminopyrimidine Analogue in Nb4 Leukemia Cells Via Down-Regulation of Birc5 Expression Publisher Pubmed



Dehghan Nayeri MJ1 ; Mahdavi M1 ; Fazeli H2 ; Hosseinpour Feizi MA1
Authors
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Authors Affiliations
  1. 1. Department of Biology, Faculty of Natural Science, University of Tabriz, Tabriz, 5166616471, Iran
  2. 2. Department of Microbiology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, 817467346, Iran

Source: Experimental Oncology Published:2019


Abstract

Aim: It has been reported that spiroaminopyrimidine derivatives inhibited the growth and proliferation of various cancer cell lines. In the present study, we evaluated cytotoxic and apoptosis-inducing effects of 2,4-diamino-1,3-diazaspiro[5.5]-9-tert-butyl-2, 4-diene-5-carbonitril (9-tBAP) on NB4 acute promyelocytic leukemia (APL) cells. Materials and Methods: The cells were treated with 10-100 µM of 9-tBAP. Cytotoxic activity of the compound was measured using the MTT assay. Apoptosis was investigated by Hoechst 33258 staining as well as by Annexin V/PI double staining. Results: The compound under study was found to be highly active cell growth inhibitor with IC50 of 30.0 ± 3.5 µM inducing apoptosis in NB4 cells. Cell cycle analysis by flow cytometry showed a time-dependent increase in sub-G1 cell population. Real-time polymerase chain reaction analysis revealed that the treatment with the compound down-regulated the BIRC5 expression in a time-dependent manner. Conclusion: 9-tBAP displayed potent anti-leukemic activity in vitro thus warranting further investigation. © Experimental Oncology, 2019
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