Piceatannol, a stilbene phytochemical, inhibits mitochondrial F0F1-ATPase activity by targeting the F1 complex

Piceatannol is a stilbene phytochemical from the seeds of Euphorbia lagasca e, previously identified as an antileukemic principle. Piceatannol is consi dered an inhibitor of several tyrosine kinases. We recently reported that r esveratrol, another stilbene phytoalexin from grape seeds, was an inhibitor of ATP synthase, Here, we demonstrated that piceatannol potently inhibited the rat brain mitochondrial F0F1-ATPase activity in both solubilized and s ubmitochondrial preparations (IC50 of 8-9 mu M), while having relatively sm all effect on the Na+, K+-ATPase activity of porcine cerebral cortex (no ef fect up to 7 mu M) Piceatannol inhibited the ATPase activity of the purifie d rat liver F1 with IC50 of about 4 mu M, while resveratrol was slightly le ss active (IC50 of about 14 mu M). Our results indicate that piceatannol an d resveratrol inhibit the F-type ATPase by targeting the F1 sector, which i s located to the inner membrane of mitochondria and plasma membrane of norm al endothelial cells and several cancer cell lines. This mechanism could po tentially contribute to the multiple effects of these chemopreventive phyto chemicals. (C) 1999 Academic Press.