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Endocrine Abstracts (2017) 49 EP925 | DOI: 10.1530/endoabs.49.EP925

ECE2017 Eposter Presentations: Pituitary and Neuroendocrinology Pituitary - Basic (13 abstracts)

Anti-proliferative effect of sodium metaarsenite (KML001) on ACTH-secreting pituitary adenoma cells

Dong Sun Kim 1 , Jung Hwan Park 1 & Yeon-Ah Sung 2

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1Department of Internal Medicine, Hanyang University College of Medicine, Seoul, Republic of Korea; 2Department of Internal Medicine, Ewha Womans University School of Medicine, Seoul, Republic of Korea.


KML001 is an orally bioavailable and water soluble trivalent arsenic compound having anti-cancer activity via controlling the numerous signaling pathways including phosphoinositide 3-kinase (PI3K)/Akt and extracellular signal-regulated kinase (ERK) signaling pathways. PI3K/Akt and ERK signaling pathways are overactivated in adrenocorticotropic hormone (ACTH)-secreting pituitary adenoma. In this study, we evaluated the effects of KML001 on cell viability, cell cycle, apoptosis, and ACTH secretion in mouse ACTH-secreting pituitary adenoma cells, AtT-20 cells. KML001 inhibited the cell viability in time-dependent and concentration-dependent manners and significantly decreased the ACTH secretion in a concentration-dependent manner. As the treatment time or treatment concentration increased, KML001 significantly increased the percentage of AtT-20 cells in apoptosis. As the treatment time or treatment concentration increased, KML001 significantly increased the percentage of AtT-20 cells in the G0/G1 phase and significantly decreased the percentage of AtT-20 cells in the S and G2/M phases. The effect of KML001 on numerous signaling pathways was determined by western blots. The phosphorylated form of Akt and mammalian target of rapamycin (mTOR) proteins were decreased in KML001-treated AtT-20 cells. The phosphorylated form of ERK protein was also decreased in KML001-treated AtT-20 cells. However, the phosphorylated form of p38 and JNK protein were increased in KML001-treated AtT-20 cells. Consequently, KML001 inhibited cell proliferation in ACTH-secreting pituitary adenoma cells via inhibition of cell cycle by inhibition of PI3K/Akt and ERK signaling pathways and induction of apoptosis by activation of p38-MAPK and JNK pathways and might reduce ACTH secretion. These results suggest that KML001 could be a candidate for the treatment of persistent or recurrent Cushing’s disease.

Volume 49

19th European Congress of Endocrinology

Lisbon, Portugal
20 May 2017 - 23 May 2017

European Society of Endocrinology 

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