TRAIL (
tumor necrosis factor-related apoptosis-inducing
ligand) is an endogenous
ligand, which plays role in immune surveillance and anti-
tumor immunity. It has ability to selectively kill
tumor cells showing no toxicity to normal cells. We tested the apoptotic and cytotoxic activities of
xanthohumol, a prenylated
chalcone found in Humulus lupulus on
androgen-sensitive human prostate
adenocarcinoma cells (LNCaP) in combination with TRAIL. Cytotoxicity was measured by
3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide tetrazolium reduction assay (MTT) and
lactate dehydrogenase assay (LDH). The expression of
death receptors (DR4/TRAIL-R1 and DR5/TRAIL-R2) and apoptosis were detected using flow cytometry. We examined mitochondrial membrane potential (ΔΨm) by DePsipher
reagent using fluorescence microscopy. The intracellular expression of
proteins was evaluated by Western blotting. Our study showed that
xanthohumol enhanced cytotoxic and apoptotic effects of TRAIL. The tested compounds activated caspases-3, -8, -9, Bid, and increased the expression of Bax. They also decreased expression of Bcl-xL and decreased mitochondrial membrane potential, while the expression of
death receptors was not changed. The findings suggest that
xanthohumol is a compound of potential use in
chemoprevention of
prostate cancer due to its sensitization of
cancer cells to TRAIL-mediated apoptosis.