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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

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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