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

Evidence-based Complementary and Alternative Medicine : ECAM
Peter KollarAleš Hampl

Abstract

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.

References

Nov 17, 2001·Current Opinion in Pharmacology·E Garattini, M Terao
Dec 25, 2003·Proceedings of the National Academy of Sciences of the United States of America·Shahab UddinAmittha Wickrema
Apr 8, 2006·Endocrine-related Cancer·S ZanardiA Decensi
Mar 3, 2010·Journal of Natural Products·Karel SmejkalKarel Dolezal
Dec 24, 2010·British Journal of Pharmacology·Peter KollárAleš Hampl
Feb 16, 2011·Journal of Natural Products·Jan HošekKarel Šmejkal
Apr 16, 2013·Nature Chemical Biology·Jaime AnguianoAna Maria Cuervo

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Citations

Oct 16, 2015·Critical Reviews in Food Science and Nutrition·José C J M D S MenezesMarc Diederich

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Methods Mentioned

BETA
scraping
flow cytometry
Protein Assay
electrophoresis
PMA

Software Mentioned

FlowJo
GraphPad Prism
Kaluza Analysis
GraphPad

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