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C Schaaf, Neuroendocrinology, Max-Planck-Institute of Psychiatry, Munich, Germany
B Shan, Neuroendocrinology, Max-Planck-Institute of Psychiatry, Munich, Germany
M Buchfelder, Neurosurgical Clinic, University of Erlangen-Nuremburg, Erlangen, Germany
M Losa, Dept. of Neurosurgery, Istituto San Raffaele, Milano, Italy
J Kreutzer, Neurosurgical Clinic, Technical University of Munich, Munich, Germany
W Rachinger, Neurosurgical Clinic, University of Munich, Munich, Germany
G Stalla, Neuroendocrinology, Max-Planck-Institute of Psychiatry, Munich, Germany
T Schilling, Dept. of Internal Medicine, University of Heidelberg, Heidelberg, Germany
E Arzt, Departamento de Fisiología y Biología Molecular y Celular, Universidad de Buenos Aires, Buenos Aires, Argentina
M Perone, Departamento de Fisiología y Biología Molecular y Celular, Universidad de Buenos Aires, Buenos Aires, Argentina
U Renner, Neuroendocrinology, Max-Planck-Institute of Psychiatry, Munich, D-80804, Germany

Correspondence: Ulrich Renner, Email: renner{at}mpipsykl.mpg.de

Abstract

Curcumin (Diferuloylmethan) is the active ingredient of the spice plant Curcuma longa and has been shown to act anti-tumourigenic in different types of tumours. Therefore we have studied its effect in pituitary tumour cell lines and adenomas. Proliferation of lactosomatotroph GH3 and somatotroph MtT/S rat pituitary cells as well as of corticotroph AtT20 mouse pituitary cells was inhibited by curcumin in monolayer cell culture and in colony formation assay in soft agar. FACS analysis demonstrated curcumin-induced cell cycle arrest at G2/M. Analysis of cell cycle proteins by immunoblotting showed reduction of Cyclin D1, CDK 4 and no change in p27kip. FACS analysis with Annexin-V-FITC/7AAD-staining demonstrated curcumin-induced early apoptosis after 3, 6, 12 and 24 h treatment and nearly no necrosis. Induction of DNA fragmentation, reduction of Bcl-2 and enhancement of cleaved caspase 3 further confirmed induction of apoptosis by curcumin. Growth of GH3 tumours in athymic nude mice was suppressed by curcumin in vivo. In endocrine pituitary tumour cell lines, GH, ACTH and PRL production was inhibited by curcumin. Studies in 25 human pituitary adenoma cell cultures have confirmed the anti-tumourigenic and hormone-suppressive effects of curcumin. Altogether, the results described in this report pose to this natural compound as a good candidate for therapeutic use on pituitary tumours.