Curcumin suppresses HIF-1A synthesis and VEGFA release in pituitary adenomas.

SHAN, B; SCHAAF, C; SCHMIDT, A; LUCIA, K; BUCHFELDER, M; LOSA, M; KUHLEN, D; KREUTZER, J; PERONE, MJ; ARZT, E; STALLA, GK; RENNER, U

JOURNAL OF ENDOCRINOLOGY

BIOSCIENTIFICA LTD

Lugar: Bristol; Año: 2012 vol. 214 p. 389 - 398

0022-0795

Curcumin (diferuloylmethane), a polyphenolic compound derived from the spice plant Curcuma longa, displays multiple actions on solid tumours; among them 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-1 alpha (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 (CoCl2 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 HIF-1. Curcumin also blocked hypoxia-induced mRNA synthesis and secretion of VEGFA in GH3 cells and 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.