Curcumin inhibits the growth, induces apoptosis and modulates the function of pituitary folliculostellate cells

SCHAAF, C; BING, S; ONOFRI, C; STALLA, GK; ARZT, E; SCHILLING, T; PERONE, MJ; RENNER, U

NEUROENDOCRINOLOGY

KARGER

Año: 2010 vol. 91 p. 200 - 210

0028-3835

The polyphenol curcumin (diferuloylmethane) is the activecomponenet of the spice plant Curcuma longa and has beenshown to exert multiple actions on mammalian cells. Wehave studied its effect on folliculostellate (FS) TtT/GF mousepituitary cells, representative of a multifunctional, endocrineinactive cell type of the anterior pituitary. Proliferationof TtT/GF cells was inhibited by curcumin in a monolayer cellculture and in the colony formation assay in soft agar. Fluorescence-activated cell-sorting (FACS) analysis demonstratedcurcumin-induced cell cycle arrest at G 2 /M accompaniedby inhibition of cyclin D 1 protein expression. Curcumin hada small effect on necrosis of TtT/GF cells, but it mainly stimulatedapoptosis as demonstrated by FACS analysis (AnnexinV-fluorescein isothiocyannate/7-aminoactinomycin D staining).Curcumin-induced apoptosis involved suppression ofBcl-2, stimulation of cleaved caspase-3 and induction of DNAfragmentation. Functional studies on FS cell-derived compounds showed that curcumin inhibited mRNA synthesisand release of angiogenic vascular endothelial growth factor-A (VEGF-A). Immune-like functions of FS cells were impairedsince curcumin downregulated Toll-like receptor 4,reduced nuclear factor-B expression and suppressed bacterialendotoxin-induced interleukin-6 (IL-6) secretion. Theinhibitory action of curcumin on VEGF-A and IL-6 productionwas also found in primary rat pituitary cell cultures, in whichFS cells are the only source of these proteins. The observedeffects of curcumin on FS cell growth, apoptosis and functionsmay have therapeutic consequences for the intrapituitaryregulation of hormone production and release as wellas for pituitary tumor pathogenesis.