Artepillin C (3,5-diprenyl-4-hydroxycinnamic acid) sensitizes LNCaP             prostate cancer cells to TRAIL-induced apoptosis.
Naturally occurring phenolic compounds have been shown to sensitize prostate             cancer cells to tumour necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced             apoptosis. TRAIL is a potent stimulator of apoptosis in cancer cells and an important             immune effector molecule in the surveillance and elimination of developing tumours.             However, many cancer cells are resistant to TRAIL-mediated death. In this study,             we aimed to determine the mechanisms by which TRAIL resistance can be overcome             in prostate cancer cells by 3,5-diprenyl-4-hydroxycinnamic acid (artepillin C).             Artepillin C is a bioactive component of Brazilian green propolis that possesses             antitumour and chemopreventive activities. TRAIL-resistant LNCaP prostate cancer             cells were treated with TRAIL and artepillin C. Cytotoxicity was measured by MTT             and lactate dehydrogenase (LDH) assays. Apoptosis was detected using Annexin V-FITC             staining by flow cytometry and fluorescence microscopy. Death receptor (DR) (TRAIL-R1/DR4             and TRAIL-R2/DR5) expression was analyzed using flow cytometry. Mitochondrial             membrane potential (∆ψm) was evaluated using DePsipher staining by fluorescence             micro-scopy. The inhibition of NF-κB (p65) activation was confirmed with the ELISA-based             TransAM NF-κB kit. Caspase-8 and caspase-3 activities were determined by colorimetric             protease assays. The results showed that artepillin C sensitized the TRAIL-resistant             LNCaP cells by engaging the extrinsic (receptor-mediated) and intrinsic (mitochondrial)             apoptotic pathways. Artepillin C increased the expression of TRAIL-R2 and decreased             the activity of NF-κB. Co-treatment with TRAIL and artepillin C induced the significant             activation of caspase-8 and caspase-3, as well as the disruption of ∆ψm. These             findings show that prostate cancer cells can be sensitized to TRAIL-mediated immunoprevention             by artepillin C and confirm the role of phenolic compounds in prostate cancer             immunochemoprevention.
Department of Microbiology and Immunology, Medical University                     of Silesia in Katowice, Zabrze, Poland.
Ewelina
E
Szliszka
Grzegorz
G
Zydowicz
Elzbieta
E
Mizgala
Wojciech
W
Krol
D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D045744:Cell Line, Tumor; D006801:Humans; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D010666:Phenylpropionates / Q000494:pharmacology*; D011471:Prostatic Neoplasms / Q000503:physiopathology* / Q000628:therapy; D053218:Receptors, Death Domain / Q000378:metabolism; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism*; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism*
D051017:Apoptosis Regulatory Proteins; D016328:NF-kappa B; D019384:Nucleic Acid Synthesis Inhibitors; D010666:Phenylpropionates; D053218:Receptors, Death Domain; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; C102259:artepillin C; D053148:Caspase 3; D053181:Caspase 8