Ursolic acid suppresses growth and ACTH secretion in AtT20 cells as a potential agent targeting on ACTH-producing pituitary adenomas

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SUN 163-194-Pituitary Disorders & Case Reports
Sunday, June 16, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SUN-188
Yingying Gong*1, Shuang Yu2, Xiaopei Cao3, Yuanyuan Liu2 and Haipeng Xiao4
1First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China, 2First Affiliated Hospital, Sun Yat-sen University, China, 3The First Affiliated Hospital of Sun Yat-sen University, 4The First Affiliated Hospital of Sun Yat-sen University, Guang Zhou, China
Adrenocorticotrophic hormone (ACTH)-producing pituitary adenomas lead to excess ACTH secretion which associated with significant mortality and impaired quality of life. To date, the first line therapy is the transphenoidal microsurgery. Considering the high recurrence rate and complications of surgery,  novel agents which directly target on pituitary adenomas and suppress hormone secretion are urgently required. In this study, the effect of ursolic acid (UA) as a candidate agent targeting on ACTH-secreting AtT20 cells (mouse corticotroph tumor cell line) pituitary was investigated. We demonstrated that UA inhibited proliferation and induced apoptosis of AtT20 cells and decreased ACTH secreation. The process of apoptosis involved in a decrease of Bcl-2/Bax ratio followed by release of mitochondria cytochrome c into the cytosol and subsequently activation of caspase-9, caspase-3/7 and caspase-8. The potential signal pathway involved c-Jun N-terminal kinase (JNK) activation but not extracellular signal-regulated protein kinases (ERK1/2) and p38 MAP kinases (p38). JNK pathway participated in UA-induced mito­chondrial apoptotic signaling transduction via increasing phosphorylation and degradation of Bcl-2, which could be partially attenuated by JNK inhibitor SP600125. In conclusion, our data suggested UA might be a promising candidate agent for the management of ACTH-producing pituitary adenomas.

Nothing to Disclose: YG, SY, XC, YL, HX

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm