Objective: To explore the effect of nuclear factor kappa-B (NF-κB) inhibitor pyrrolidine dithiocarbamate (PDTC) on the proliferation and apoptosis of acute leukemia cell HL-60.
Methods: HL-60 cells were cultured with PDTC of 0, 25, 50, 100 μmol/L for 24, 48, 72 h. The inhibition rate of cell proliferation was detected by CCK-8 assay. Cell apoptosis was detected by Hoechst staining. Cell cycle was detected by flow cytometry. The expression of B-cell lymphoma-2 (BCL-2), BCL-2 associated X protein (BAX), cyclinD1, activated cysteinyl aspartate specific proteinase (cleaved caspase 3), cleaved caspase 8 and activation of NF-κB signal pathway related protein was detected by Western blot.
Results: After the HL-60 cells were cultured with PDTC of 25, 50, 100 μmol/L for 24, 48, 72 h, the inhibition rate of cell proliferation increased with the enhancement of PDTC concentration at the same time point (r=0.924, P<0.01). At the same PDTC concentration, the inhibition rate of cell proliferation increased with prolonging of time (r=0.952, P<0.01). After HL-60 cell was cultured with PDTC of 25, 50, 100 μmol/L for 48 h, compared with control group, PDTC of 25, 50, 100 μmol/L increased the cell apoptotic rate, arrested cell cycle at G1 phase (P<0.01), the expression of BCL-2, cyclinD1 and p-NF-κB p65 was down-regulated(P<0.05), the expression of BAX, cleaved caspase 3, cleaved caspase 8 was up-regulated(P<0.01). PDTC of 50, 100 μmol/L down-regulated the expression of p-inhibitor of NF-κB (p-IκBα)(P<0.01).
Conclusion: PDTC can inhibit acute leukemia HL-60 cell proliferation and induce cell apoptosis.
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http://dx.doi.org/10.19746/j.cnki.issn.1009-2137.2020.05.018 | DOI Listing |
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Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina.
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Despite significant advancements with combination anti-retroviral agents, eradicating human immunodeficiency virus (HIV) remains a challenge due to adverse effects, adherence issues, and emerging viral resistance to existing therapies. This underscores the urgent need for safer, more effective drugs to combat resistant strains and advance acquired immunodeficiency syndrome (AIDS) therapeutics. Eight triterpene esters (1-8) were identified from Uncaria rhynchophylla hooks.
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Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
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