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.
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.
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DOI：
10.3390/ijms17060837
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发表时间：
2016-06-22
影响因子：
5.6
通讯作者：
Szliszka E
中科院分区：
文献类型：
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作者：
Kłósek M;Mertas A;Król W;Jaworska D;Szymszal J;Szliszka E
TRAIL （tumor necrosis factor-related apoptosis-inducing ligand，肿瘤坏死因子相关凋亡诱导配体）是一种内源性配体，具有免疫监视和抗肿瘤免疫功能。具有选择性杀伤肿瘤细胞的能力，对正常细胞无毒性。我们测试了黄腐酚（一种在葎草中发现的烯基查尔酮）联合TRAIL对雄激素敏感的人前列腺癌细胞（LNCaP）的凋亡和细胞毒活性。采用3-（4,5-二甲基噻唑-2-基）-2,5-二苯四唑溴化四唑还原试验（MTT）和乳酸脱氢酶试验（LDH）测定细胞毒性。流式细胞术检测死亡受体DR4/TRAIL-R1和DR5/TRAIL-R2的表达及凋亡情况。我们用荧光显微镜用DePsipher试剂检测线粒体膜电位（ΔΨm）。Western blotting检测细胞内蛋白表达。我们的研究表明，黄腐酚增强了TRAIL的细胞毒性和凋亡作用。这些化合物激活了caspase -3、-8、-9、Bid，增加了Bax的表达。同时降低Bcl-xL的表达，降低线粒体膜电位，而死亡受体的表达没有变化。研究结果表明，黄腐酚是一种潜在的用于前列腺癌化学预防的化合物，因为它能使癌细胞对trail介导的细胞凋亡敏感。
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.