Growing evidence supports the critical role of lipid peroxidation products in the control of cell proliferation.In previous studies we demonstrated the e fficient restriction of the proliferation rate in several cell lines resulting from the in vitro treatment with endogenous lipid polar components of cell membranes.Among these,9-hydroxystearic acid (9-HSA),a primary intermediate of lipid peroxidation,induced a signi ficant arrest in G0/G1 in HT29 colon cancer cells.In response to 9-HSA treatment of HT29 we observed cell growth arrest and increase in p21 WAF1 expression both at the transcriptional and the translational levels.Growth of p21 WAF1 -deleted HCT116 human colon carcinoma cells was not inhibited by 9-HSA.We present evidence that p21 WAF1 is required for 9-HSA mediated growth arrest in human colon carcinoma cells. 2003 Elsevier Inc.All rights reserved.