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.