Department of Nutrition, Faculty of Medicine, University of Oslo, POB 1046, Blindern, N-0316, Oslo, Norway.
ICMR-National Institute of Nutrition, Hyderabad, Telangana, 500007, India.
Cell Biol Int. 2020 May;44(5):1237-1251. doi: 10.1002/cbin.11324. Epub 2020 Feb 26.
Curcumin has a protective role in placental diseases like preeclampsia and preterm birth. Very little is known about its functional effects on growth, angiogenesis, and epigenetic activities of human first trimester placenta. HTR8/SVneo trophoblasts cells were used as model for human first trimester placenta. Effects of curcumin (≥80%) in these cells were investigated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), radioactive thymidine uptake, quantitative real-time polymerase chain reaction (qRT-PCR), promoter DNA methylation, qRT-PCR array, tube formation, wound healing, and immunoblot assays. PC3 (prostate cancer), JEG-3 (trophoblast), and HMEC-1 (endothelial) cells were used as control in various experiments. Unlike in PC3 cells, curcumin stimulated growth, proliferation, and viability in HTR8/SVneo cells. Curcumin increased tube formation, and messenger RNA (mRNA) expression of angiogenic factors such as vascular endothelial growth factor A (VEGFA) and protein expression of proangiogenic factor VEGF receptor-2 and fatty acid-binding protein-4 (FABP4) in these cells. Curcumin-stimulated tube formation was associated with an increased expression of VEGFR2 and FABP4. The stimulatory effects of curcumin were inhibited by VEGFR2 (SU5416) and FABP4 (BMS309403) inhibitors. Curcumin also significantly increased both mRNA and protein expression of HLA-G in HTR8/SVneo cells. Curcumin increased mRNA expression of DNMT3A and NOTCH signaling system whereas down-regulated mRNA expression of HSD11β2. Curcumin enhanced hypomethylation of gene promoters against oxidative stress and DNA damage pathway mediators. Curcumin promotes cell growth, migration, and thus angiogenic potential of these cells. Increased expression of HLA-G by curcumin, hitherto unknown, is a novel finding since HLA-G not only favors the immune environment for invasive trophoblasts but also positively modulates angiogenesis.
姜黄素在子痫前期和早产等胎盘疾病中具有保护作用。然而，人们对其在人类早期胎盘的生长、血管生成和表观遗传活性方面的功能影响知之甚少。HTR8/SVneo 滋养细胞被用作人类早期胎盘的模型。使用 3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐（MTT）、放射性胸苷摄取、实时定量聚合酶链反应（qRT-PCR）、启动子 DNA 甲基化、qRT-PCR 阵列、管形成、划痕愈合和免疫印迹分析来研究姜黄素（≥80%）在这些细胞中的作用。PC3（前列腺癌）、JEG-3（滋养细胞）和 HMEC-1（内皮）细胞在各种实验中用作对照。与 PC3 细胞不同，姜黄素刺激 HTR8/SVneo 细胞的生长、增殖和活力。姜黄素增加了这些细胞中的管形成以及血管内皮生长因子 A（VEGFA）等血管生成因子的信使 RNA（mRNA）表达和促血管生成因子 VEGF 受体-2 和脂肪酸结合蛋白-4（FABP4）的蛋白表达。姜黄素刺激的管形成与 VEGFR2 和 FABP4 的表达增加有关。VEGFR2（SU5416）和 FABP4（BMS309403）抑制剂抑制了姜黄素的刺激作用。姜黄素还显著增加了 HTR8/SVneo 细胞中 HLA-G 的 mRNA 和蛋白表达。姜黄素增加了 DNMT3A 和 NOTCH 信号系统的 mRNA 表达，而下调了 HSD11β2 的 mRNA 表达。姜黄素增强了基因启动子的低甲基化，从而对抗氧化应激和 DNA 损伤途径介质。姜黄素促进这些细胞的细胞生长、迁移和血管生成潜力。姜黄素增加 HLA-G 的表达，这是一个新的发现，因为 HLA-G 不仅有利于侵袭性滋养细胞的免疫环境，而且还积极调节血管生成。
