Pokeweed antiviral protein (PAP) is a plant-derived, highly potent ribosome inactivating protein that causes inhibition of protein translation and rapid cell death. We have previously described potent cytotoxic activity of a GnRH (gonadotropin-releasing hormone) receptor-targeted conjugate protein (GnRH-PAP) and demonstrated that cytotoxicity depended on the number of GnRH receptors and the duration of exposure. Here, we demonstrate that the GnRH-PAP conjugate was cytotoxic to three different prostate cancer cell lines, supporting the feasibility of using such hormonotoxins as novel therapeutics for hormone-responsive cancers such as prostate cancer.