Effects of resveratrol on the G(0)-G(1) transition and cell cycle progression of mitogenically stimulated human lymphocytes.
Resveratrol (RSV) has been suggested to have cancer preventive properties, on the basis that it suppresses proliferation and induces apoptosis in various tumor cells. Here we test its cytostatic effects on peripheral blood human lymphocytes. RSV (up to 50 microM) had no detectable effects on resting lymphocytes. With the mitogen phytohemagglutin (PHA), however, RSV elicited concentration- and time-dependent responses in lymphocytes. RSV (>/=50 microM) prevented cell entry into the cell cycle, resulting in 99% suppression at 100 microM. The arrested lymphocytes following 24h treatment with 50 microM RSV had minimal RNA content, the feature characteristic of G(0) cells, and were blocked at the stage past the induction of cyclins D2 and D3 and prior to induction of cyclin E. Prolonged treatment (72h) of PHA-stimulated lymphocytes with 100 microM RSV showed a pronounced decrease in the expression of pRb, cyclins E and B, and reduction in p34cdc2 and PCNA. The activation-induced apoptosis was also reduced in the presence of >/=50 microM RSV. These data suggest that studies designed to test RSV efficacy as a chemopreventive agent should include evaluation of its immunomodulatory effect revealed by suppression of lymphocyte stimulation as well as its effect on apoptosis of stimulated lymphocytes.
Hsieh
Tze
T
Brander Cancer Research Institute, New York Medical College, Hawthorne, NY 10532, USA.
Halicka
Dorota
D
Lu
Xiaohua
X
Kunicki
Jan
J
Guo
Junqiao
J
Darzynkiewicz
Zbigniew
Z
Wu
Joseph
J
D000165:Acridine Orange / Q000494:pharmacology; D020533:Angiogenesis Inhibitors / Q000494:pharmacology; D017209:Apoptosis; D015153:Blotting, Western; D002453:Cell Cycle; D002455:Cell Division; D056742:Cyclin D2; D056743:Cyclin D3; D019927:Cyclin E / Q000378:metabolism; D016213:Cyclins / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D005434:Flow Cytometry; D016193:G1 Phase / Q000187:drug effects*; D006801:Humans; D007150:Immunohistochemistry; D008214:Lymphocytes / Q000378:metabolism*; D008934:Mitogens / Q000494:pharmacology*; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D012313:RNA / Q000378:metabolism; D016192:Resting Phase, Cell Cycle / Q000187:drug effects*; D000077185:Resveratrol; D016160:Retinoblastoma Protein / Q000378:metabolism; D013267:Stilbenes / Q000494:pharmacology*; D013997:Time Factors
D020533:Angiogenesis Inhibitors; C080336:CCND2 protein, human; C534696:CCND3 protein, human; D056742:Cyclin D2; D056743:Cyclin D3; D019927:Cyclin E; D016213:Cyclins; D008934:Mitogens; D018809:Proliferating Cell Nuclear Antigen; D016160:Retinoblastoma Protein; D013267:Stilbenes; D012313:RNA; D004247:DNA; D000165:Acridine Orange; D000077185:Resveratrol