Interplay between the intracellular energy sensor AMP-activated protein kinase (AMPK) and the estrogen receptor activities in regulating rat pituitary tumor cell (GH3) growth in vitro

AMPK (AMP-activated protein kinase) is one of the key players in maintaining intracellular homoeostasis. AMPK is well known as an energy sensor and can be activated by increased intracellular AMP levels. Generally, the activation of AMPK turns on catabolic pathways that generate ATP, while inhibiting cell proliferation and biosynthetic processes that consume ATP. In recent years, intensive investigations on the regulation and the function of AMPK indicates that AMPK not only functions as an intracellular energy sensor and regulator, but is also a general stress sensor that is important in maintaining intracellular homoeostasis during many kinds of stress challenges. In the present paper, we will review recent literature showing that AMPK functions far beyond its proposed energy sensor and regulator function. AMPK regulates ROS (reactive oxygen species)/redox balance, autophagy, cell proliferation, cell apoptosis, cellular polarity, mitochondrial function and genotoxic response, either directly or indirectly via numerous downstream pathways under physiological and pathological conditions.

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Apotransferrins from several species promote thyroid hormone-dependent rat pituitary tumor cell growth in iron-restricted serum-free defined culture

Molecular and Cellular Endocrinology ◽

10.1016/0303-7207(92)90164-2 ◽

1992 ◽

Vol 83 (2-3) ◽

pp. 239-251 ◽

Cited By ~ 7

Author(s):

Hidetaka Sato ◽

John E. Eby ◽

Rajbabu Pakala ◽

David A. Sirbasku

Keyword(s):

Thyroid Hormone ◽

Cell Growth ◽

Tumor Cell ◽

Pituitary Tumor ◽

Tumor Cell Growth ◽

Serum Free ◽

Rat Pituitary ◽

Defined Culture ◽

Pituitary Tumor Cell

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Pituitary Tumor Suppression by Combination of Cabergoline and Chloroquine

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2017-00627 ◽

2017 ◽

Vol 102 (10) ◽

pp. 3692-3703 ◽

Cited By ~ 9

Author(s):

Shao Jian Lin ◽

Ze Rui Wu ◽

Lei Cao ◽

Yong Zhang ◽

Zhi Gen Leng ◽

...

Keyword(s):

Tumor Cell ◽

Cell Lines ◽

Pituitary Adenomas ◽

Pituitary Tumor ◽

Human Cancer ◽

Primary Cultures ◽

Human Pituitary ◽

Pituitary Tumor Cell

Abstract Context The dopamine agonist cabergoline (CAB) has been used widely in the treatment of prolactinomas and other types of pituitary adenomas, but its clinical use is hampered by intolerance in some patients with prolactinoma and lack of effectiveness in other pituitary tumor types. Chloroquine (CQ) is an old drug widely used to treat malaria. Recent studies, including our own, have revealed that CAB and CQ are involved in induction of autophagy and activation of autophagic cell death. Objective To test whether CAB and CQ can function cooperatively to suppress growth of pituitary adenomas as well as other cancers. Results In vitro studies using the rat pituitary tumor cell lines MMQ and GH3, human pituitary tumor cell primary cultures, and several human cancer cell lines showed that CQ enhanced suppression of cell proliferation by CAB. These results were confirmed in in vivo xenograft models in nude mice and estrogen-induced rat prolactinomas. To understand the mechanism of combined CAB and CQ action, we established a low-CAB-dose condition in which CAB was able to induce autophagy but failed to suppress cell growth. Addition of CQ to low-dose CAB blocked normal autophagic cycles and induced apoptosis, evidenced by the further accumulation of p62/caspase-8/LC3-II. Conclusion The data suggest that combined use of CAB and CQ may increase clinical effectiveness in treatment of human pituitary adenomas, as well as other cancers, making it an attractive option in tumor and cancer therapies.

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