Fang Qixiang, Que Taotao, Liu Bo, Dan Weichao, Wei Yi, Ren Bingyi, Fan Yizeng, Hou Tao, Zeng Jin
Department of Urology, The First Affiliated Hospital of Xi'an Jiaotong University, 710061 Xi'an, Shaanxi, China.
Department of Medicine, Xi'an Jiaotong University, 710061 Xi'an, Shaanxi, China.
Front Biosci (Landmark Ed). 2022 Dec 28;27(12):335. doi: 10.31083/j.fbl2712335.
β-ionone is a terminal cyclic analog of beta-carotenoids widely found in plants. In recent years, accumulating evidence has shown that β-ionone exerts antitumor effects on various malignant tumors. However, limited studies have revealed the role of β-ionone in regulating the epithelial-mesenchymal transition (EMT) of prostate cancer (PCa) cells. This study aimed to investigate the effect of β-ionone on the EMT process of PCa, focusing on Wnt/β-catenin signaling pathway.
After exposure to β-ionone, cell viability was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and the Brdu proliferation assay. The Transwell and wounding healing were used to investigate the migration and invasion abilities of PCa cells. Expression of proteins involved in the EMT process (E-cadherin, N-cadherin, vimentin) and proteins in the Wnt/β-catenin pathway (β-catenin, GSK3-β, and p-GSK3-β) were explored by western blotting. The effects of β-ionone on β-catenin degradation were explored by cycloheximide tracking assay and ubiquitination assay. Nude mouse xenograft model was served as the model system .
The migration, invasion, and EMT process of PCa Human PC-3 prostate adenocarcinoma cells (PC3) and Human 22RV1 prostate adenocarcinoma cells (22RV1) cells were significantly inhibited after β-ionone treatment. In addition, β-ionone also inhibited the growth and EMT process of subcutaneous xenograft tumors in nude mice. The study also found that β-catenin, which promotes EMT, was downregulated after β-ionone treatment. Further mechanistic studies revealed that β-ionone inhibited the Wnt/β-catenin pathway by accelerating the ubiquitination and degradation of β-catenin in PCa, thus inhibiting the downstream migration, invasion, and EMT processes.
These findings demonstrate that β-ionone may be a potential natural compound targeting the Wnt/β-catenin pathway for the treatment of PCa.
β-紫罗兰酮是β-胡萝卜素的末端环状类似物，广泛存在于植物中。近年来，越来越多的证据表明β-紫罗兰酮对多种恶性肿瘤具有抗肿瘤作用。然而，关于β-紫罗兰酮在调节前列腺癌细胞上皮-间质转化（EMT）中的作用的研究较少。本研究旨在探讨β-紫罗兰酮对前列腺癌EMT过程的影响，重点关注Wnt/β-连环蛋白信号通路。
用β-紫罗兰酮处理细胞后，通过3-(4,5-二甲基噻唑-2)-2,5-二苯基四氮唑溴盐（MTT）法和溴脱氧尿苷（Brdu）增殖试验测定细胞活力。采用Transwell和划痕愈合实验研究前列腺癌细胞的迁移和侵袭能力。通过蛋白质印迹法检测EMT过程相关蛋白（E-钙黏蛋白、N-钙黏蛋白、波形蛋白）和Wnt/β-连环蛋白信号通路中的蛋白（β-连环蛋白、糖原合成酶激酶3-β（GSK3-β）和磷酸化糖原合成酶激酶3-β（p-GSK3-β））的表达。通过环己酰亚胺追踪试验和泛素化试验研究β-紫罗兰酮对β-连环蛋白降解的影响。以裸鼠异种移植模型作为模型系统。
β-紫罗兰酮处理后，人前列腺癌PC-3细胞（PC3）和人22RV1前列腺腺癌细胞（22RV1）的迁移、侵袭及EMT过程均受到显著抑制。此外，β-紫罗兰酮还抑制了裸鼠皮下异种移植瘤的生长和EMT过程。研究还发现，促进EMT的β-连环蛋白在β-紫罗兰酮处理后表达下调。进一步的机制研究表明，β-紫罗兰酮通过加速前列腺癌中β-连环蛋白的泛素化和降解来抑制Wnt/β-连环蛋白信号通路，从而抑制下游的迁移、侵袭和EMT过程。
这些研究结果表明，β-紫罗兰酮可能是一种潜在的天然化合物，可靶向Wnt/β-连环蛋白信号通路用于治疗前列腺癌。
