Modulation of anti-adhesion molecule MUC-1 is associated with arctiin-induced growth inhibition of PC-3 cells

BACKGROUND. Lignans have been reported to possess anti-tumor activity in various cancer cells. However, their anticancer effects in human prostate cancer have not been well established. Here, we examine the effect of arctiin, a lignan compound, on growth regulation in prostate cancer PC-3 cells. We postulated that arctiin modulates the attachment/detachment of PC-3 cells and we investigated the role of arctiin on MUC-1 expression. METHODS. The effect of arctiin on PC-3 cell growth was examined using an MTT assay method and cell number was calculated by means of a standard regression line. The expressions of MUC-1 and integrins alpha(2), alpha(5), and beta(1) were detected using FACScan flow cytometric analysis. Levels of MUC-1 mRNA were determined using reverse transcriptase PCR (RT-PCR). RESULTS. Treatment of PC-3 cells with arctiin decreased the cell number in a concentration and time-dependent manner in serum-containing condition. Arctiin preferentially induced cell detachment, but did not have anti-proliferation or cytotoxic effects in PC-3 cells. The arctiin-induced effect was inhibited by cycloheximide, indicating that protein synthesis was required. FACScan flow cytometric analysis demonstrated that arctiin increased the expression of the anti-adhesion mucin MUC-1, but did not affect integrin expression in PC-3 cells. The arctiin-induced increase in MUC-1 protein expression was due to up-regulation of mRNA, as revealed by RT-PCR analysis. CONCLUSIONS. Arctiin significantly induces cell detachment and decreases the cell numbers via the up-regulation of MUC-1 mRNA and protein in PC-3 cells. (C) 2003 Wiley-Liss. Inc.