Impact of curcumin on growth and apoptosis of pituitary tumor cells

SCHAAF, C.; PERONE, M.J.; LABEUR, M.; THEODOROPOULOU, M.; CORREA-DE-SANTANA, E.; ARZT, E.; STALLA, G.K.; RENNER, U.

Bamberg, Alemania

Congreso; 12th Annual Meeting of the Neuroendocrinology Section of the DGE; 2008

Curcumin (Diferuoylmethan) is the active ingredient in the traditional herbal remedy and dietary spice turmeric (Curcuma longa). Curcumin has a wide range of beneficial properties, including anti-inflammatory, antioxidant, chemopreventive and chemotherapeutic activity. The pleiotropic activities of curcumin derive from its ability to influence multiple signaling pathways. We have investigated in vitro effects of curcumin in lactosomatotroph GH3 and somatotroph MtT/S rat pituitary cells, in corticotroph AtT20 mouse pituitary cells and in folliculostellate TtT/GF mouse pituitary cells. Curcumin inhibited growth of all cell lines in monolayer cell culture and suppressed colony formation in soft agar (IC50:19μM). At least for GH3 cells it could be shown, that GH3 cell tumor formation was reduced by curcumin in nude mice. FACS analysis with Annexin-V-FITC/7AAD-staining demonstrated curcumin-induced early apoptosis after 12 and 24h treatment and nearly no necrosis. In endocrine cell types, hormone production was inhibited by curcumin. Angiogenic components (VEGF, VEGF receptor type 2, HIF-1alpha) and immunomodulatory factors (IL-6, TLr4) were all suppressed by curcumin in pituitary cells. Regarding the mechanism of action, results indicate that curcumin suppresses the PI3 kinase/Akt pathway and inhibits CDK4. Reduction of Bcl-2 and enhancement of cleaved caspase 9 suggest induction of apoptosis by curcumin, which was confirmed by cell death ELISA. In summary, curcumin shows clear anti-tumorigenic properties and its effects on human pituitary tumors will be tested in future studies.