Enhydrin Exhibits Antitumor Effects on Human Prostate Cancer Cells Associated with Reduced PI3K/AKT- and NF-κB-Related Gene and Protein Expression

Enhydrin, a melampolide-type sesquiterpene lactone abundant in the leaves of yacon (Smallanthus sonchifolius), has not previously been investigated for its anti-prostate cancer activity. This study investigated the antiproliferative effects of enhydrin in human prostate cancer cells, its regulatory effects on apoptosis-related molecules, and its impact on the PI3K/AKT and NF-κB signaling pathways. Three prostate cancer cell lines (PC3, DU145, and LNCaP) were treated with enhydrin, and its effects were analyzed using cell viability assays, morphological observation, flow cytometry, apoptosis-focused TaqMan qPCR array, qRT-PCR, and Western blotting. In vivo antitumor activity was assessed in a PC3 xenograft mouse model. Enhydrin reduced cell viability in a dose- and time-dependent manner, induced morphological changes associated with cytotoxicity, and caused G1 cell-cycle arrest. Gene expression analysis revealed downregulation of PI3K/AKT- and NF-κB-related genes and modulation of BCL2 family genes toward a pro-apoptotic profile, which was confirmed at both mRNA and protein levels. In vivo, enhydrin suppressed tumor growth without significant body-weight loss. These findings suggest that enhydrin exerts antitumor effects in prostate cancer by reducing the expression of PI3K/AKT and NF-κB related molecules and modulating apoptosis-related proteins. Although additional studies are required to determine pathway activity, directly confirm apoptosis, and evaluate normal-cell cytotoxicity and the therapeutic window, these findings provide preliminary biological evidence of the effects of enhydrin in prostate cancer models.