Acanthopanax trifoliatus (L) Merr (AT) is commonly used as an herbal medicine and edible plant in someareas of China and other Asian countries. AT is thought to have anticancer effects, but potential mechanismsremain unknown. To assess the anticancer properties of AT, we exposed prostate cancer cells to AT extracts andassessed cell proliferation and signaling pathways. An ethanol extract of AT was suspended in water followed bysequential extraction with petroleum ether, ethyl acetate and n-butanol. PC-3 cells were treated with differentconcentrations of each extract and cell viability was determined by the MTT and trypan blue exclusion assays.The ethyl acetate extract of the ethanol extract had a stronger inhibitory effect on growth and a strongerstimulatory effect on apoptosis than any of the other extracts. Mechanistic studies demonstrated that the ethylacetate extract suppressed the transcriptional activity of NF-kB, increased the level of caspase-3, and decreasedthe levels of phospho-Erk1/2 and phospho-Akt. This is the first report on the anticancer activity of AT in culturedhuman prostate cancer cells. The results suggest that AT can provide a plant-based medicine for the treatmentor prevention of prostate cancer.