The tumor suppressor protein p53 plays an important role in the protection against the development of cancer and is inactivated in many human malignancies. Since p53 is an important inhibitor of cell growth, keeping p53 function under control is critical for survival of cell. One of the principal mechanisms by which cells achieve this is by regulating the p53 protein level, although its phosphorylation and cellular localization also contribute to the regulation of its function. Since many tumors secrete growth factor(s) that inhibit apoptosis and support the growth of cancer cells, we wanted to know whether insulin would have an effect on antitumor and p53-inducing activities of human tumor necrosis factor-alpha (TNF-alpha). Here we show that treatment of human cervical carcinoma cell line, ME-180S, with TNF-alpha results in time-dependent accumulation of p53 and its transcriptional target, p21. However, pretreatment of these cells with insulin inhibits TNF-alpha-dependent cell killing, induction of p53, p21 and apoptosis.