Accumulating epidemiological data suggest that Asian men have lower incidences of prostate cancer and benign prostate hyperplasia (BPH) compared with American and European populations and may have benefited from their higher intake of phytoestrogens in their diet. However, how these phytochemicals affect prostatic diseases is still unclear. In this study, we isolated six lignans from a plant, Campylotropis hirtella (Franch.) Schindl., which has been used as a folk medicine for treatment of BPH in China, through bioassay guided fractionation. They were dehydrodiconiferyl alcohol (C1), 4-[(-6-hydroxy-2,3-dihydro-1-benzofuran-3-yl)methyl]-5-methoxybenzene-1,3-diol (C2), erythro-guaiacylglycerol-beta-O-4'-coniferyl ether (C3), threo-guaiacylglycerol-beta-O-4'-coniferyl ether (C4), secoisolariciresinol (C5), and prupaside (C6), where C2 was identified as a new lignan analog. Their IC50 values for inhibition of prostate specific antigen (PSA) secretion were 19, 45, 110, 128, 137, and 186 microM, respectively, from C1 to C6 in LNCaP cells. Further study showed that C1-5 down-regulated cellular PSA expression and C1-4 also decreased androgen receptor (AR) expression in LNCaP cells. Furthermore, we investigated the proapoptotic effect of C1 on LNCaP cells. The active forms of caspase 3 associated with the specific proteolysis of poly (ADP-ribose) polymerase (PARP) were detected, and the antiapoptotic protein Bcl-2 was down-regulated after the treatment with C1. These results collectively indicated that these lignans may have chemopreventive or therapeutic actions for prostate cancer through suppressing AR signaling pathway and inducing apoptosis.