Flavonoid 4'-O-Methylkuwanon E from Morus alba Induces the Differentiation of THP-1 Human Leukemia Cells.
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.
Department of Human Pharmacology and Toxicology, Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences Brno, Palackého Třída 1-3, 612 42 Brno, Czech Republic.
Peter
0000-0003-2265-1528
P
Kollar
Department of Histology and Embryology, Faculty of Medicine, Masaryk University, Kamenice 3, 625 00 Brno, Czech Republic ; International Clinical Research Center, St. Anne's University Hospital, Pekařská 53, 656 91 Brno, Czech Republic.
Tomáš
T
Bárta
Department of Human Pharmacology and Toxicology, Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences Brno, Palackého Třída 1-3, 612 42 Brno, Czech Republic.
Stanislava
S
Keltošová
Department of Human Pharmacology and Toxicology, Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences Brno, Palackého Třída 1-3, 612 42 Brno, Czech Republic.
Pavlína
P
Trnová
Department of Human Pharmacology and Toxicology, Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences Brno, Palackého Třída 1-3, 612 42 Brno, Czech Republic.
Veronika
V
Müller Závalová
Department of Molecular Biology and Pharmaceutical Biotechnology, Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences Brno, Palackého Třída 1-3, 612 42 Brno, Czech Republic.
Karel
K
Šmejkal
Department of Molecular Biology and Pharmaceutical Biotechnology, Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences Brno, Palackého Třída 1-3, 612 42 Brno, Czech Republic.
Jan
0000-0003-0975-1671
J
Hošek
International Clinical Research Center, St. Anne's University Hospital, Pekařská 53, 656 91 Brno, Czech Republic ; Department of Cytokinetics, Institute of Biophysics, Academy of Sciences of the Czech Republic, Královopolská 135, 612 65 Brno, Czech Republic.
Radek
R
Fedr
International Clinical Research Center, St. Anne's University Hospital, Pekařská 53, 656 91 Brno, Czech Republic ; Department of Cytokinetics, Institute of Biophysics, Academy of Sciences of the Czech Republic, Královopolská 135, 612 65 Brno, Czech Republic.
Karel
K
Souček
Department of Histology and Embryology, Faculty of Medicine, Masaryk University, Kamenice 3, 625 00 Brno, Czech Republic.
Aleš
A
Hampl