Effects of berberine on the secretion of cytokines and expression of genes involved in cell cycle regulation in THP-1 monocytic cell line

Mohammadi, Saeed and Seyedhoseini, Fakhri Sadat and Asadi, Jahanbakhsh and Yazdani, Yaghoub (2017) Effects of berberine on the secretion of cytokines and expression of genes involved in cell cycle regulation in THP-1 monocytic cell line. Iranian Journal of Basic Medical Sciences, 20 (5). pp. 530-537.

[img]
Preview
Text
IJBMS_Volume 20_Issue 5_Pages 530-537.pdf

Download (1MB) | Preview
Official URL: http://ijbms.mums.ac.ir/article_8677.html

Abstract

Objective(s): Current acute myeloid leukemia (AML) therapeutic strategies have irreversible side-effects. Berberine (BBR) is an isoquinoline alkaloid, which has been known as an aryl hydrocarbon receptor (AhR) ligand. AhR is a cytoplasmic receptor, which is involved in the regulation of cellular and immune responses. Here, we investigated the expression profile of genes involved in the cell cycle and different cytokines upon BBR-mediated AhR activation on AML THP-1 cell line. Materials and Methods: THP-1 cells and normal monocytes were treated with different concentrations of BBR (10 μM, 25 μM, 50 μM, and 100 μM) for 24 and 48 hr. The cell viability was measured by MTT assay. Real-time RT-PCR was conducted to evaluate the expression of AhR, cytochrome P450 1A1 (CYP1A1), interleukin 1 beta (IL1β), p21, p27, cyclin-dependent kinase 2 (CDK2) and p53. Cellular expression of AhR was also assessed using immunofluorescence method. ELISA was used to determine the level of IL-10 and IL-12 cytokines. Results: BBR inhibits the proliferation of THP-1 cells in a dose- and time-dependent manner with minimal toxicity on normal monocytes. Phorbol 12-myristate 13-acetate (PMA) treatment increased the cellular expression of AhR. The AhR target genes (CYP1A1, IL1β) were overexpressed upon BBR treatment. BBR downregulated Cdk2 and upregulated p21, p27 and p53 genes in THP-1 cells. IL-10 was significantly increased upon BBR treatment, while IL-12 was not significantly changed in all combinations. Conclusion: BBR could be introduced as an effective chemotherapeutic agent against AML by giving rise to the expression of CDK inhibitors and anti-inflammatory cytokines and downregulation of CDK2.

Item Type: Article
Subjects: QV pharmacology
Divisions: Journals > Iranian J Basic Medical Sciences
Depositing User: ijbms ijbms
Date Deposited: 22 Sep 2017 19:59
Last Modified: 22 Sep 2017 19:59
URI: http://eprints.mums.ac.ir/id/eprint/2493

Actions (login required)

View Item View Item