This paper explores the use of proteomics as a tool for identifying protein species whose expression has been altered by dibenzoylmethane (DBM) in LNCaP cells. Although DBM, a constituent of licorice, has been shown to induce cell cycle arrest and regulate androgen receptor (AR) expression, the mechanism by which these events occur is unknown. To develop a better understanding of the effect of DBM on cancer cells, we analyzed changes in protein expression induced by DBM in LNCaP cells using two-dimensional (2-D) gel electrophoresis. The proteomic approach used to study LNCaP cells has lead to the analysis and identification of a number of protein species that increase or decrease as a result of exposure to DBM. In particular, twenty features were found to be differentially expressed in this study based on the quantitation of two separate 2-D-fluorescence difference gel electrophoresis analyses. Thirteen of these features were identified through mass spectrometric analysis. The intensity of 10 out of the 13 spots identified increased 2- to 3-fold in response to 25 micro M and 50 micro M DBM and the remaining three spots decreased 2-fold in response to the same DBM treatment. This study investigates proteomic changes induced by treatment of cells with DBM in order to develop a model for the mechanism by which DBM induces cell cycle arrest and represses AR expression.