Bergamot (Citrus bergamia Risso) fruit extracts as γ-globin gene expression inducers: phytochemical and functional perspectives.
Epicarps of Citrus bergamia fruits from organic farming were extracted with the objective of obtaining derived products differently rich in coumarins and psoralens. The extracts were chemically characterized by (1)H nuclear magnetic resonance (NMR), gas chromatography-flame ionization detection (GC-FID), gas chromatography-mass spectrometry (GC-MS), and high-pressure liquid chromatography (HPLC) for detecting and quantifying the main constituents. Both bergamot extracts and chemical standards corresponding to the main constituents detected were then assayed for their capacity to increase erythroid differentiation of K562 cells and expression of γ-globin genes in human erythroid precursor cells. Three experimental cell systems were employed: (a) the human leukemic K562 cell line, (b) K562 cell clones stably transfected with a pCCL construct carrying green-enhanced green fluorescence protein (EGFP) under the γ-globin gene promoter, and (c) the two-phase liquid culture of human erythroid progenitors isolated from healthy donors. The results suggest that citropten and bergapten are powerful inducers of differentiation and γ-globin gene expression in human erythroid cells. These data could have practical relevance, because pharmacologically mediated regulation of human γ-globin gene expression, with the consequent induction of fetal hemoglobin, is considered to be a potential therapeutic approach in hematological disorders, including β-thalassemia and sickle cell anemia.
Guerrini
Alessandra
A
Department of Biology and Evolution, Agro-technological and Pharmaceutical Resources, Agri-Unife, University of Ferrara, Ferrara, Italy.
Lampronti
Ilaria
I
Bianchi
Nicoletta
N
Zuccato
Cristina
C
Breveglieri
Giulia
G
Salvatori
Francesca
F
Mancini
Irene
I
Rossi
Damiano
D
Potenza
Rocco
R
Chiavilli
Francesco
F
Sacchetti
Gianni
G
Gambari
Roberto
R
Borgatti
Monica
M
D002454:Cell Differentiation / Q000187:drug effects; D002957:Citrus / Q000737:chemistry*; D004912:Erythrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D015672:Erythroid Precursor Cells / Q000187:drug effects / Q000378:metabolism; D005638:Fruit / Q000737:chemistry*; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D020014:K562 Cells; D010936:Plant Extracts / Q000737:chemistry* / Q000494:pharmacology*; D012333:RNA, Messenger / Q000097:blood; D055545:gamma-Globins / Q000235:genetics*
D010936:Plant Extracts; D012333:RNA, Messenger; D055545:gamma-Globins