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Growth suppression of mouse pituitary corticotroph tumor AtT20 cells by curcumin: a model for treating Cushing's disease. PLoS One 2010 Apr 13;5(4):e9893

Date

04/21/2010

Pubmed ID

20405005

Pubmed Central ID

PMC2854133

DOI

10.1371/journal.pone.0009893

Scopus ID

2-s2.0-77956297954   13 Citations

Abstract

BACKGROUND: Pituitary corticotroph tumors secrete excess adrenocorticotrophic hormone (ACTH) resulting in Cushing's disease (CD). Standard treatment includes surgery and, if not successful, radiotherapy, both of which have undesirable side effects and frequent recurrence of the tumor. Pharmacotherapy using PPARgamma agonists, dopamine receptor agonists, retinoic acid or somatostatin analogs is still experimental. Curcumin, a commonly used food additive in South Asian cooking, has potent growth inhibitory effects on cell proliferation. Our laboratory recently demonstrated that curcumin inhibited growth and induced apoptosis in prolactin- and growth hormone-producing tumor cells. Subsequently, Schaaf et.al. confirmed our findings and also showed the in vivo effectiveness of curcumin to suppress pituitary tumorigenesis. However the molecular mechanism that mediate this effect of curcumin are still unknown.

PRINCIPAL FINDINGS: Using the mouse corticotroph tumor cells, AtT20 cells, we report that curcumin had a robust, irreversible inhibitory effect on cell proliferation and clonogenic property. The curcumin-induced growth inhibition was accompanied by decreased NFkappaB activity. Further, curcumin down-regulated the pro-survival protein Bcl-xL, depolarized the mitochondrial membrane, increased PARP cleavage, which led to apoptotic cell death. Finally, curcumin had a concentration-dependent suppressive effect on ACTH secretion from AtT20 cells.

CONCLUSION: The ability of curcumin to inhibit NFkappaB and induce apoptosis in pituitary corticotroph tumor cells leads us to propose developing it as a novel therapeutic agent for the treatment of CD.

Author List

Bangaru ML, Woodliff J, Raff H, Kansra S

Author

Hershel Raff PhD Professor in the Medicine department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

ACTH-Secreting Pituitary Adenoma
Adrenocorticotropic Hormone
Animals
Antineoplastic Agents
Apoptosis
Cell Line, Tumor
Cell Proliferation
Curcumin
Dose-Response Relationship, Drug
Mice
NF-kappa B
Pituitary ACTH Hypersecretion
jenkins-FCD Prod-484 8aa07fc50b7f6d102f3dda2f4c7056ff84294d1d