Curcumin acts as anti-tumorigenic and hormone-suppressive agent in murine and human pituitary tumour cells in vitro and in vivo

SCHAAF, C.; SHAN, B; BUCHFELDER, M; LOSA, M; KREUTZER, J; RACHINGER, W; STALLA, GK; SCHILLING, T; ARZT, E; PERONE, MJ; RENNER, U

ENDOCRINE - RELATED CANCER

BIOSCIENTIFICA LTD

Año: 2009 vol. 16 p. 1339 - 1350

1351-0088

Curcumin (diferuloylmethane) is the active ingredient of the spice plant Curcuma longa and hasbeen shown to act anti-tumorigenic in different types of tumours. Therefore, we have studied itseffect in pituitary tumour cell lines and adenomas. Proliferation of lactosomatotroph GH3 andsomatotroph MtT/S rat pituitary cells as well as of corticotroph AtT20 mouse pituitary cells wasinhibited by curcumin in monolayer cell culture and in colony formation assay in soft agar.Fluorescence-activated cell sorting (FACS) analysis demonstrated curcumin-induced cellcycle arrest at G2/M. Analysis of cell cycle proteins by immunoblotting showed reductionin cyclin D1, cyclin-dependent kinase 4 and no change in p27kip. FACS analysis with AnnexinV-FITC/7-aminoactinomycin D staining demonstrated curcumin-induced early apoptosis after 3,6, 12 and 24 h treatment and nearly no necrosis. Induction of DNA fragmentation, reduction ofBcl-2 and enhancement of cleaved caspase-3 further confirmed induction of apoptosis bycurcumin. Growth of GH3 tumours in athymic nude mice was suppressed by curcumin in vivo.In endocrine pituitary tumour cell lines, GH, ACTH and prolactin production were inhibitedby curcumin. Studies in 25 human pituitary adenoma cell cultures have confirmed the antitumorigenicand hormone-suppressive effects of curcumin. Altogether, the results describedin this report suggest this natural compound as a good candidate for therapeutic use onpituitary tumours.