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 muM) had no detectable effects on resting lymphocytes. With the mitogen phytohemagglutin (PHA), however, RSV elicited concentration- and time-dependent responses in lymphocytes. RSV (greater than or equal to50 muM) prevented cell entry into the cell cycle, resulting in 99% suppression at 100 muM. The arrested lymphocytes following 24 h treatment with 50 muM RSV had minimal RNA content, the feature characteristic of Go cells, and were blocked at the stage past the induction of cyclins D2 and D3 and prior to induction of cyclin E. Prolonged treatment (72 h) of PHA-stimulated lymphocytes with 100 muM 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 greater than or equal to50 muM 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. (C) 2002 Elsevier Science (USA). All rights reserved.