Neuroendocrinology Group, Max Planck Institute of Psychiatry, Kraepelinstraße 10, D-80804 Munich, Germany.
J Endocrinol. 2012 Sep;214(3):389-98. doi: 10.1530/JOE-12-0207. Epub 2012 Jun 27.
Curcumin (diferuloylmethane), a polyphenolic compound derived from the spice plant Curcuma longa, displays multiple actions on solid tumours including anti-angiogenic effects. Here we have studied in rodent and human pituitary tumour cells the influence of curcumin on the production of hypoxia inducible factor 1α (HIF1A) and vascular endothelial growth factor A (VEGFA), two key components involved in tumour neovascularisation through angiogenesis. Curcumin dose-dependently inhibited basal VEGFA secretion in corticotroph AtT20 mouse and lactosomatotroph GH3 rat pituitary tumour cells as well as in all human pituitary adenoma cell cultures (n=32) studied. Under hypoxia-mimicking conditions (CoCl(2) treatment) in AtT20 and GH3 cells as well as in all human pituitary adenoma cell cultures (n=8) studied, curcumin strongly suppressed the induction of mRNA synthesis and protein production of HIF1A, the regulated subunit of the hypoxia-induced transcription factor HIF1. Curcumin also blocked hypoxia-induced mRNA synthesis and secretion of VEGFA in GH3 cells and in all human pituitary adenoma cell cultures investigated (n=18). Thus, curcumin may inhibit pituitary adenoma progression not only through previously demonstrated anti-proliferative and pro-apoptotic actions but also by its suppressive effects on pituitary tumour neovascularisation.
姜黄素（双阿魏酰甲烷），一种来源于香料植物姜黄的多酚化合物，对实体瘤具有多种作用，包括抗血管生成作用。在这里，我们研究了姜黄素对缺氧诱导因子 1α（HIF1A）和血管内皮生长因子 A（VEGFA）产生的影响，这两种因子是通过血管生成参与肿瘤新生血管形成的关键成分。姜黄素在不同剂量下可抑制促皮质素 AtT20 小鼠和生长激素 GH3 大鼠垂体肿瘤细胞以及所有研究的人类垂体腺瘤细胞培养物（n=32）中的基础 VEGFA 分泌。在 AtT20 和 GH3 细胞以及所有研究的人类垂体腺瘤细胞培养物（n=8）中模拟缺氧条件（CoCl2 处理）下，姜黄素强烈抑制 HIF1A（缺氧诱导转录因子 HIF1 的调节亚基）的 mRNA 合成和蛋白产生的诱导。姜黄素还阻断了 GH3 细胞和所有研究的人类垂体腺瘤细胞培养物（n=18）中缺氧诱导的 VEGFA mRNA 合成和分泌。因此，姜黄素不仅可以通过先前证明的抗增殖和促凋亡作用，还可以通过抑制垂体肿瘤新生血管生成来抑制垂体腺瘤的进展。
