Objective: A diet rich in natural antioxidants in combination with anticancer therapy is important in reducing morbidity and mortality in addition to diminishing toxicity and side effects of chemotherapeutic agents. Cisplatin (cis-diamminedichloroplatinum II, cis-Pt) is a common chemotherapeutic agent, but it causes side effects, including hematologic toxicity with changes in the biological function of blood cells. Methods: We compared the action of two phenolic compounds isolated from the bark of Yucca schidigera: trans-3,3',5,5'-tetrahydroxy-4'-methoxystilbene and resveratrol (trans-3,4',5-trihydroxystilbene, present also in grapes and wine) on oxidative stress induced by cisplatin (used in chemotherapy) and selenium-cisplatin conjugate ([NH3](2)Pt(SeO3 [Se-Pt], with a slight toxic effect on blood cells) in human blood platelets and peripheral blood lymphocytes. Results:. The trans-3,3',5,5'-tetrahydroxy-4'-methoxystilbene, like resveratrol, significantly inhibited protein carbonylation (measured by enzyme-linked immunosorbent assay and western blot analysis) in blood platelets treated with platinum compounds (10 mu g/mL) and markedly reduced oxidation of thiol groups of proteins in these cells. The trans-3,3',5,5'-tetrahydroxy-4'-methoxystilbene, like resveratrol, caused a distinct reduction of platelet lipid peroxidation induced by platinum compounds. The combined action of the tested phenolic compounds with Se-Pt evoked a significant decrease in DNA damage (measured by the comet assay) in lymphocytes compared with cells treated with. Se-Pt only. Conclusion: We conclude that one promising natural product may be trans-3,3',5,5'-tetrahydroxy-4'-methoxystilbene, because it is a stronger antioxidant in the tested models in vitro compared with resveratrol (P < 0.05). The trans-3,3',5,5'-tetrahydroxy-4'-methoxystilbene can also be useful as a protective factor against platinum compounds during chemotherapy or cancer prophylaxis. (C) 2006 Elsevier Inc. All rights reserved.