Department of Nutritional Science, Fu Jen Catholic University, Taipei, Taiwan.
Division of Urology, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
Sci Rep. 2019 Nov 21;9(1):17267. doi: 10.1038/s41598-019-53509-3.
The secreted frizzled-related protein 5 gene (SFRP5) that antagonize the Wnt/β-catenin signaling is frequently inactivated by promoter methylation and oncogenic activation of the Wnt signaling pathway is common in many cancers. The curcumin-rich Curcuma longa has been reported to potent anti-cancer property involved in epigenetic regulation to inhibit tumor suppressor gene methylation and re-expression. In a compounds screening, we found that curcumin can inhibit Wnt/β-catenin signaling. Therefore, the aim of this study was to investigate the effects of curcumin on SFRP5 DNA methylation modification in an ovarian cancer cell line (SKOV3). SKOV3 cells were treated with DMSO, 10 μM 5-aza-2'-deoxycytidine (DAC), 5 μM DAC, 20 μM curcumin, and 20 μM curcumin combined with 5 μM DAC for 96 hours, following which RNA and proteins were extracted for further analysis. The results showed that curcumin combined with 5 μM DAC may inhibit cancer cell colony formation, migration through EMT (epithelial-mesenchymal transition) process regulation, total DNMT activity, especially in DNMT3a protein expression, and may also regulate tumor suppressor gene SFRP5 expression involved in the Wnt/β-catenin signaling pathway. The combined treatment attenuated ovarian cancer development.
分泌卷曲相关蛋白 5 基因（SFRP5）可拮抗 Wnt/β-连环蛋白信号通路，其启动子甲基化失活和致癌性的 Wnt 信号通路激活在许多癌症中很常见。姜黄富含姜黄素，已被报道具有潜在的抗癌特性，涉及表观遗传调控，抑制肿瘤抑制基因甲基化和再表达。在化合物筛选中，我们发现姜黄素可以抑制 Wnt/β-连环蛋白信号通路。因此，本研究旨在探讨姜黄素对卵巢癌细胞系（SKOV3）中 SFRP5 DNA 甲基化修饰的影响。用 DMSO、10μM 5-氮杂-2′-脱氧胞苷（DAC）、5μM DAC、20μM 姜黄素和 20μM 姜黄素联合 5μM DAC 处理 SKOV3 细胞 96 小时，提取 RNA 和蛋白质进行进一步分析。结果表明，姜黄素联合 5μM DAC 可能通过 EMT（上皮-间充质转化）过程调节抑制癌细胞集落形成和迁移，总 DNMT 活性，特别是 DNMT3a 蛋白表达，也可能调节肿瘤抑制基因 SFRP5 的表达，参与 Wnt/β-连环蛋白信号通路。联合治疗可减轻卵巢癌的发展。
