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 line HL-60. A concentration as low as 30 microM 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.
Ragione
F D
FD
Medical School, Second University of Naples, Naples, Italy. dellarag@cds.unina.it
Cucciolla
V
V
Borriello
A
A
Pietra
V D
VD
Racioppi
L
L
Soldati
G
G
Manna
C
C
Galletti
P
P
Zappia
V
V
D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects*; D004261:DNA Replication / Q000187:drug effects; D016195:G2 Phase / Q000187:drug effects*; D018922:HL-60 Cells; D006801:Humans; D000077185:Resveratrol; D016196:S Phase / Q000187:drug effects*; D013267:Stilbenes / Q000494:pharmacology*
D016588:Anticarcinogenic Agents; D013267:Stilbenes; D000077185:Resveratrol