1. Induction of apoptosis in human acute monocytic leukemia (THP-1) cells with NaF and the related mechanisms.
- Author
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Jiang H, Fang P, and Zhang G
- Subjects
- Cell Proliferation drug effects, Humans, Leukemia, Monocytic, Acute drug therapy, Leukemia, Monocytic, Acute enzymology, Tumor Cells, Cultured, Apoptosis drug effects, Cariostatic Agents pharmacology, Gene Expression Regulation, Enzymologic drug effects, Gene Expression Regulation, Neoplastic drug effects, Leukemia, Monocytic, Acute pathology, Sodium Fluoride pharmacology, Ubiquitin-Activating Enzymes metabolism
- Abstract
Purpose: Acute monocytic leukemia remains a big challenge, and there are a series of non-specific esterases which can be inhibited by sodium fluoride (NaF) in mononuclear cells, providing insights into the leukemia targeted therapy. In this study, the apoptotic effect of NaF with human mononuclear leukemia THP-1 cells and the inhibition of α-naphthol acetate esterase (α-NAE) activity, and also the potentially underlying mechanisms were investigated., Methods: THP-1 cells were cultured with different concentrations of NaF (0, 0.5, 1, 2, 4, 8 mM) for 24, 48 and 72 hrs. The α-NAE staining and chromogenic method were used to detect the activation of α-NAE. The 3-(4, 5-dimethylthiazol-2-yl)-2), 5-diphenyltetrazolium bromide (MTT) assay was used to detect the antitumor effect of NaF on THP-1 cells in vitro. Flow cytometry was used to observe the apoptotic ratio following treatment with NaF in THP-1 cells. The mRNA levels of mammalian target of Bcl-2 and Bax were detected pre and post-NaF treatment using reverse transcription polymerase chain reaction (RT-PCR)., Results: The generation of depression effects of THP-1 cells cultured in vitro were detected using MTT technology, which revealed a dose- and time-dependent association. After 24hrs of exposure to NaF at greater than 1mmol/L, typical apoptotic changes were observed, accompanied by the α-NAE positive reaction and decreased intensity. The IC50 was 4 mmol/L at 24hrs. Flow cytometric analysis indicated that treatment with NaF at concentrations of 2, 4 and 8 mmol/L increased the apoptotic rate of THP-1 cells. RT-PCR indicated that NaF upregulated the gene expression of Bax and downregulated the expression of Bcl-2., Conclusion: NaF inhibited the proliferation of THP-1 cells and the activation of α-NAE by adversely regulating the expression of Bax and Bcl-2.
- Published
- 2018