Curcumin suppresses HIF1A 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 compoundderived from the spice plant Curcuma longa, displays multipleactions on solid tumours including anti-angiogenic effects.Herewe have studied in rodent and human pituitary tumour cells theinfluence of curcumin on the production of hypoxia induciblefactor 1a (HIF1A) and vascular endothelial growth factor A(VEGFA), two key components involved in tumour neovascularisationthrough angiogenesis. Curcumin dose-dependentlyinhibited basal VEGFA secretion in corticotroph AtT20 mouseand lactosomatotroph GH3 rat pituitary tumour cells as well asin all human pituitary adenoma cell cultures (nZ32) studied.Under hypoxia-mimicking conditions (CoCl2 treatment) inAtT20 and GH3 cells as well as in all human pituitary adenomacell cultures (nZ8) studied, curcumin strongly suppressed theinduction of mRNA synthesis and protein production ofHIF1A, the regulated subunit of the hypoxia-inducedtranscription factor HIF1. Curcumin also blocked hypoxiainducedmRNAsynthesisand secretion ofVEGFAinGH3 cellsand in all human pituitary adenoma cell cultures investigated(nZ18). Thus, curcumin may inhibit pituitary adenomaprogression not only through previously demonstrated antiproliferativeand pro-apoptotic actions but also by its suppressiveeffects on pituitary tumour neovascularisation.