Resveratrol Arrests the Cell Division Cycle at S/G2 Phase Transition

Resveratrol (3,5,4′-trihydroxystilbene) is a naturally occurring phytoalexin, found in grapes and wine, which has been reported to exert a variety of important pharmacological effects. We have investigated the activity of resveratrol on proliferation and differentiation of the promyelocitic cell lin...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 1998-09, Vol.250 (1), p.53-58
Main Authors: Ragione, Fulvio Della, Cucciolla, Valeria, Borriello, Adriana, Pietra, Valentina Della, Racioppi, Luigi, Soldati, Giuliana, Manna, Caterina, Galletti, Patrizia, Zappia, Vincenzo
Format: Article
Language:English
Subjects:
Anticarcinogenic Agents - pharmacology
CELL CULTURE
CELL DIFFERENTIATION
Cell Differentiation - drug effects
Cell Division - drug effects
CELL LINES
CELL PROLIFERATION
CULTIVO DE CELULAS
CULTURE DE CELLULE
DIFERENCIACION CELULAR
DIFFERENCIATION CELLULAIRE
DNA Replication - drug effects
FARMACOLOGIA
G2 Phase - drug effects
HL-60 Cells
Humans
PHARMACOLOGIE
PHARMACOLOGY
S Phase - drug effects
Stilbenes - pharmacology
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Summary:Resveratrol (3,5,4′-trihydroxystilbene) is a naturally occurring phytoalexin, found in grapes and wine, which has been reported to exert a variety of important pharmacological effects. We have investigated the activity of resveratrol on proliferation and differentiation of the promyelocitic cell line HL-60. A concentration as low as 30 μM causes a complete arrest of proliferation and a rapid induction of differentiation towards a myelo-monocytic phenotype. Analyses by flow cytometry showed the absence of the G2/M peak and the accumulation of cells in G1 and S phases. Moreover, at the concentrations employed, a very low amount of apoptotic cells was evidenced. A detailed biochemical analysis demonstrated that the G1 phase of the cell division cycle engine was completely unmodified by resveratrol addition, thus indicating that the G1 → S transition occurs normally. Conversely, after only 24 h treatment, a significant increase of cyclins A and E could be observed along with the accumulation of cdc2 in the inactive phosphorylated form. These data demonstrate that resveratrol causes a complete and reversible cell cycle arrest at the S phase checkpoint.
ISSN:0006-291X
1090-2104
DOI:10.1006/bbrc.1998.9263