Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand-Induced Apoptosis in Prostate Cancer Cells after Treatment with Xanthohumol-A Natural Compound Present in Humulus lupulus L.

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.

International journal of molecular sciences. 2016 Jun 22*** epublish ***

Małgorzata Kłósek, Anna Mertas, Wojciech Król, Dagmara Jaworska, Jan Szymszal, Ewelina Szliszka

Chair and Department of Microbiology and Immunology, School of Medicine with Division of Dentistry in Zabrze, Medical University of Silesia in Katowice, Jordana 19, 41-808 Zabrze, Poland. ., Chair and Department of Microbiology and Immunology, School of Medicine with Division of Dentistry in Zabrze, Medical University of Silesia in Katowice, Jordana 19, 41-808 Zabrze, Poland. ., Chair and Department of Microbiology and Immunology, School of Medicine with Division of Dentistry in Zabrze, Medical University of Silesia in Katowice, Jordana 19, 41-808 Zabrze, Poland. ., Chair and Department of Microbiology and Immunology, School of Medicine with Division of Dentistry in Zabrze, Medical University of Silesia in Katowice, Jordana 19, 41-808 Zabrze, Poland. ., Department of Production Engineering, Faculty of Materials Engineering and Metallurgy, Silesian University of Technology, Krasińskiego 8b, 40-019 Katowice, Poland. ., Chair and Department of Microbiology and Immunology, School of Medicine with Division of Dentistry in Zabrze, Medical University of Silesia in Katowice, Jordana 19, 41-808 Zabrze, Poland. .

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