Curcumin inhibits the growth, induces apoptosis and modulates the function of pituitary folliculostellate cells.
The polyphenol curcumin (diferuloylmethane) is the active componenet of the spice plant Curcuma longa and has been shown to exert multiple actions on mammalian cells. We have studied its effect on folliculostellate (FS) TtT/GF mouse pituitary cells, representative of a multifunctional, endocrine inactive cell type of the anterior pituitary. Proliferation of TtT/GF cells was inhibited by curcumin in a monolayer cell culture and in the colony formation assay in soft agar. Fluorescence-activated cell-sorting (FACS) analysis demonstrated curcumin-induced cell cycle arrest at G(2)/M accompanied by inhibition of cyclin D(1) protein expression. Curcumin had a small effect on necrosis of TtT/GF cells, but it mainly stimulated apoptosis as demonstrated by FACS analysis (Annexin V-fluorescein isothiocyannate/7-aminoactinomycin D staining). Curcumin-induced apoptosis involved suppression of Bcl-2, stimulation of cleaved caspase-3 and induction of DNA fragmentation. Functional studies on FS cell-derived compounds showed that curcumin inhibited mRNA synthesis and release of angiogenic vascular endothelial growth factor-A (VEGF-A). Immune-like functions of FS cells were impaired since curcumin downregulated Toll-like receptor 4, reduced nuclear factor-kappaB expression and suppressed bacterial endotoxin-induced interleukin-6 (IL-6) secretion. The inhibitory action of curcumin on VEGF-A and IL-6 production was also found in primary rat pituitary cell cultures, in which FS cells are the only source of these proteins. The observed effects of curcumin on FS cell growth, apoptosis and functions may have therapeutic consequences for the intrapituitary regulation of hormone production and release as well as for pituitary tumor pathogenesis.
Schaaf
Christian
C
Max Planck Institute of Psychiatry, Neuroendocrinology Group, Munich, Germany.
Shan
Bing
B
Onofri
Chiara
C
Stalla
Günter K
GK
Arzt
Eduardo
E
Schilling
Tobias
T
Perone
Marcelo J
MJ
Renner
Ulrich
U
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D003474:Curcumin / Q000494:pharmacology*; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D051379:Mice; D010903:Pituitary Gland, Anterior / Q000166:cytology* / Q000187:drug effects*; D010911:Pituitary Neoplasms; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D015850:Interleukin-6; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; C467498:vascular endothelial growth factor A, rat; D003474:Curcumin