Abstract
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.
Highlights
Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL) is a type II transmembrane protein identified by S
We have shown that xanthohumol can enhance apoptosis induced by TRAIL in cancer cells [42,43]
After treatment of prostate cancer cells with TRAIL and/or xanthohumol we analyzed the expression of proteins
Summary
TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) is a type II transmembrane protein identified by S. We have shown that xanthohumol can enhance apoptosis induced by TRAIL in cancer cells [42,43]. After treatment of prostate cancer cells with TRAIL and/or xanthohumol we analyzed the expression of proteins. RCeystoutlotxsic and Apoptotic Activities of Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL) in Androgen-Sensitive Human Prostate Adenocarcinoma Cells (LNCaP). Similar results were obtained by Delmulle et al [61], who applied 200 μM xanthohumol or other prenylflavonoids (isoxanthohumol, 8-prenylnaringenin, and 6-prenylnaringenin) and incubated PC-3 prostate cancer cells with prenylflavonoids for 15, 30, 60, 90, and 120 min They demonstrated that the investigated compounds did not activate caspase-3. Combination of TRAIL with xanthohumol activates caspases-3, -8, and -9 in LNCaP cells. Xanthohumol used alone did not affect the expression of proapoptotic proteins Bid and Bax of LNCaP cancer cells. A similar result was obtained by Siddiqui et al [58] after the incubation of LNCaP prostate cancer cells with TRAIL and EGCG, and by Kim et al [68] after treatment of DU-145 prostate cancer cells with TRAIL and quercetin
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