Flavonoid 4 '-O-Methylkuwanon E from Morus alba Induces the Differentiation of THP-1 Human Leukemia Cells

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Authors

KOLLAR Peter BÁRTA Tomáš KELTOŠOVÁ Stanislava TRNOVÁ Pavlína ZÁVALOVÁ MÜLLER Veronika ŠMEJKAL Karel HOŠEK Jan FEDR Radek SOUČEK Karel HAMPL Aleš

Year of publication 2015
Type Article in Periodical
Magazine / Source Evidence-based Complementary and Alternative Medicine
MU Faculty or unit

Faculty of Medicine

Citation
Doi http://dx.doi.org/10.1155/2015/251895
Field Genetics and molecular biology
Keywords ACTIVATED PROTEIN-KINASE; RETINOIDS; INHIBITION; PATHWAYS
Description Aims. In this work we studied cytodifferentiation effects of newly characterized prenyl flavonoid 4'-O-methylkuwanon E (4ME) isolated from white mulberry (Morus alba L.). Main Methods. Cell growth and viability were measured by dye exclusion assay; cell cycle and surface antigen CD11b were monitored by flow cytometry. For the cytodifferentiation of cells the NBT reduction assay was employed. Regulatory proteins were assessed by western blotting. Key Findings. 4ME induced dose-dependent growth inhibition of THP-1 cells, which was not accompanied by toxic effect. Inhibition of cells proliferation caused by 4ME was associated with the accumulation in G1 phase and with downregulation of hyperphosphorylated pRb. Treatment with 4ME led to significant induction of NBT-reducing activity of PMA stimulated THP-1 cells and upregulation expression of differentiation-associated surface antigen CD11b. Our results suggest that monocytic differentiation induced by 4ME is connected with up-regulation of p38 kinase activity. Significance. Our study provides the first evidence that 4ME induces the differentiation of THP-1 human monocytic leukemia cells and thus is a potential cytodifferentiating anticancer agent.
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