Wu Ting-Feng, Hsu Li-Ting, Tsang Bo-Xian, Huang Li-Chien, Shih Wan-Yin, Chen Li-Yi
Department of Biotechnology Southern Taiwan University of Science and Technology, 1 Nan-Tai Street, YungKang District, 710, Tainan, Taiwan.
BMC Complement Altern Med. 2016 Mar 9;16:96. doi: 10.1186/s12906-016-1071-7.
Pomegranate fruit has been shown to exhibit the inhibitory activity against prostate cancer and lung cancer in vitro and in vivo, which might be a resource for chemoprevention and chemotherapy of cancer. Our previous documented findings indicated that treatment of urinary bladder urothelial carcinoma cell with the ethanol extract isolated from the juice of pomegranate fruit grown in Taiwan could inhibit tumor cell. In this study we intended to uncover the molecular pathway underlying anti-cancer efficacy of Taiwan pomegranate fruit juice against urinary bladder urothelial carcinoma.
We exploited two-dimensional gel electrophoresis coupled with tandem mass spectrometry to find the de-regulated proteins. Western immunoblotting was used to confirm the results collected from proteomics study.
Comparative proteomics indicated that 20 proteins were differentially expressed in ethanol extract-treated T24 cells with 19 up-regulated and 1 down-regulated proteins. These de-regulated proteins were involved in apoptosis, cytoskeleton regulation, cell proliferation, proteasome activity and aerobic glycolysis. Further studies on signaling pathway demonstrated that ethanol extract treatment might inhibit urinary bladder urothelial carcinoma cell proliferation through restriction of PTEN/AKT/mTORC1 pathway via profilin 1 up-regulation. It also might evoke cell apoptosis through Diablo over-expression.
The results of this study provide a global picture to further investigate the anticancer molecular mechanism of pomegranate fruit.
石榴果实已被证明在体外和体内均表现出对前列腺癌和肺癌的抑制活性，这可能是癌症化学预防和化疗的一种资源。我们之前记录的研究结果表明，用从台湾种植的石榴果实汁液中分离出的乙醇提取物处理膀胱尿路上皮癌细胞可抑制肿瘤细胞。在本研究中，我们旨在揭示台湾石榴果汁对膀胱尿路上皮癌抗癌功效的分子途径。
我们利用二维凝胶电泳结合串联质谱法来寻找失调的蛋白质。蛋白质免疫印迹法用于确认从蛋白质组学研究中收集的结果。
比较蛋白质组学表明，在乙醇提取物处理的T24细胞中有20种蛋白质差异表达，其中19种上调，1种下调。这些失调的蛋白质涉及细胞凋亡、细胞骨架调节、细胞增殖、蛋白酶体活性和有氧糖酵解。对信号通路的进一步研究表明，乙醇提取物处理可能通过上调丝切蛋白1限制PTEN/AKT/mTORC1通路来抑制膀胱尿路上皮癌细胞增殖。它还可能通过上调暗黑破坏神蛋白引发细胞凋亡。
本研究结果为进一步研究石榴果实的抗癌分子机制提供了全面的图景。
