Previous studies have shown that the proanthocyanidin-mediated induction of apoptosis and arrest of the cell cycle in cancer cells was associated with up-regulation of p21 Cip1/WAF1 (p21), suggesting that p21 may be the molecular mediator of the observed effects. Here we show that procyanidins induce a rapid and sustained arrest of the cell cycle, and increase apoptosis, concomitant with an increase in p21 expression. However, blocking the PA-induced up-regulation of p21 expression with siRNA did not alter PA-mediated changes in apoptosis and cell cycle, demonstrating that p21 is not responsible for the PA-induced effects.