Abstract
Matrine, a natural product extracted from the root of Sophora flavescens, is a promising alternative drug in different types of cancer. Here, we aimed to investigate the therapeutic effects and underlying molecular mechanisms of matrine on human acute lymphoblastic leukemia (ALL) cell line, CCRF-CEM. Cell viability and IC50 values were determined by WST-1 cell cytotoxicity assay. Cell cycle distribution and apoptosis rates were analyzed by flow cytometry. Expression patterns of 44 selected miRNAs and 44 RNAs were analyzed by quantitative reverse transcription polymerase chain reaction (qRT-PCR) using the Applied Biosystems 7500 Fast Real-Time PCR System. Matrine inhibited cell viability and induced apoptosis of CCRF-CEM cells in a dose-dependent manner. Cell cycle analysis demonstrated that matrine-treated CCRF-CEM cells significantly accumulated in the G0/G1 phase compared with the untreated control cells. hsa-miR-376b-3p (-37.09 fold, p = 0.008) and hsa-miR-106b-3p (-16.67 fold, p = 0.028) expressions were decreased, whereas IL6 (95.47 fold, p = 0.000011) and CDKN1A (140.03 fold, p = 0.000159) expressions were increased after matrine treatment. Our results suggest that the downregulation of hsa-miR-106b-3p leads to the upregulation of target p21 gene, CDKN1A, and plays a critical role in the cell cycle progression by arresting matrine-treated cells in the G0/G1 phase.
Highlights
T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive form of leukemia characterized by an increased proliferation of lymphoblasts
Human T-ALL cell line CCRF-CEM was obtained from the American Type Culture Collection (ATCC, Manassas, VA, USA) and cultured in RPMI-1640 medium supplemented with 10% Fetal bovine serum (FBS), 100 units/mL penicillin, and 100 μg/mL streptomycin and L-glutamine
Our results indicate that matrine at concentrations of 0.5-2.0 mg/ml does not affect the viability of CCRF-CEM cells
Summary
T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive form of leukemia characterized by an increased proliferation of lymphoblasts. T-ALL constitutes 10-15% of childhood ALLs and 25% of adult ALLs. An effective chemotherapy combination for T-ALL has not been developed yet, and firstline therapy fails in 25% of pediatric and more than 50% of adult cases [1,2]. Recent studies have demonstrated that new treatments targeting specific genes or molecular pathways in cancer patients are more efficient and less toxic. Targeted treatment and the determination of related oncogenes have a priority in terms of patient survival and occurrence of toxicity [2]. New treatment options should be developed for these cases by determining new molecular targets
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