title: Ursolic acid suppresses growth and adrenocorticotrophic hormone secretion in AtT20 cells as a potential agent targeting adrenocorticotrophic hormone-producing pituitary adenoma.
abstract: Adrenocorticotrophic hormone (ACTH)-producing pituitary adenoma leads to excess ACTH secretion, which is associated with significant mortality and impaired quality of life. Thus far, the first line therapy is the transphenoidal microsurgery. Considering the high recurrence rate and complications of surgery, novel agents, which directly target on pituitary ACTH-producing adenoma and suppress ACTH secretion are urgently required. In the present study, the effect of ursolic acid (UA) as a candidate agent targeting ACTH-producing AtT20 cells was investigated. It was demonstrated that UA inhibited the viability and induced apoptosis of AtT20 cells and decreased ACTH secretion. The process of apoptosis involved a decrease of the B cell lymphoma 2 (Bcl-2)/Bcl2-associated X protein ratio followed by a release of mitochondrial cytochrome c into the cytosol with subsequent activation of caspase-9, -3/7 and -8. The potential signaling pathway involved the activation of c-Jun N-terminal kinase (JNK) but not extracellular signal-regulated protein kinases1/2 and p38 mitogen-activated protein kinase. The JNK pathway participated in UA-induced mitochondrial apoptotic signaling transduction via increasing the phosphorylation and degradation of Bcl-2, which may be partly attenuated by the JNK inhibitor SP600125. In conclusion, the present study indicates that UA may be a promising candidate agent for the management of ACTH-producing pituitary adenoma.
authors.affiliation: Department of Endocrinology, The First Affiliated Hospital of Sun Yat‑Sen University, Guangzhou, Guangdong 510080, P.R. China.
authors.forename: Ying-Ying
authors.initials: YY
authors.lastname: Gong
authors.affiliation: Department of Endocrinology, The First Affiliated Hospital of Sun Yat‑Sen University, Guangzhou, Guangdong 510080, P.R. China.
authors.forename: Yuan-Yuan
authors.initials: YY
authors.lastname: Liu
authors.affiliation: Department of Endocrinology, The First Affiliated Hospital of Sun Yat‑Sen University, Guangzhou, Guangdong 510080, P.R. China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Yu
authors.affiliation: Department of Pharmacology, Zhong‑Shan School of Medicine, Sun Yat‑Sen University, Guangzhou, Guangdong 510080, P.R. China.
authors.forename: Xiao-Nan
authors.initials: XN
authors.lastname: Zhu
authors.affiliation: Department of Endocrinology, The First Affiliated Hospital of Sun Yat‑Sen University, Guangzhou, Guangdong 510080, P.R. China.
authors.forename: Xiao-Pei
authors.initials: XP
authors.lastname: Cao
authors.affiliation: Department of Endocrinology, The First Affiliated Hospital of Sun Yat‑Sen University, Guangzhou, Guangdong 510080, P.R. China.
authors.forename: Hai-Peng
authors.initials: HP
authors.lastname: Xiao
mesh_terms: D049913:ACTH-Secreting Pituitary Adenoma / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D000324:Adrenocorticotropic Hormone / Q000378:metabolism*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D014315:Triterpenes / Q000494:pharmacology*; D000097245:Ursolic Acid
chemical_list: D000324:Adrenocorticotropic Hormone; D000972:Antineoplastic Agents, Phytogenic; D014315:Triterpenes; D000097245:Ursolic Acid