4.3 Article

Matrine induced G0/G1 arrest and apoptosis in human acute T-cell lymphoblastic leukemia (T-ALL) cells

Journal

BOSNIAN JOURNAL OF BASIC MEDICAL SCIENCES
Volume 18, Issue 2, Pages 141-149

Publisher

ASSOC BASIC MEDICAL SCI FEDERATION BOSNIA & HERZEGOVINA SARAJEVO
DOI: 10.17305/bjbms.2017.2457

Keywords

Sophora flavescens; matrine; acute lymphoblastic leukemia; T-ALL; CCRF-CEM; miR-376b; miR-106b; p21; CDKN1A; cell cycle; G0/G1 arrest; apoptosis; autophagy

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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 G(0)/G(1) phase compared with the untreated control cells. hsa-miR-376b-3p (-37.09 fold, p = 0.008) and hsa-miR106b- 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 G(0)/G(1) phase.

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