AT-101 acts as anti-proliferative and hormone suppressive agent in mouse pituitary corticotroph tumor cells
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Date
2018
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Abstract
Purpose: Gossypol, a naturally occurring compound in cottonseeds, has anticancer effects against several tumor cell lines. It has been extensively studied in clinical trials and is well tolerated with a favorable safety profile. AT-101, a derivative of R (−)-gossypol, binds to Bcl-2 family proteins and induces apoptosis in vitro. Although transsphenoidal surgical excision of the pituitary corticotroph adenoma is the gold standard of care, it is not successful all the time. Medical therapy for Cushing’s disease still remains a challenge for the clinicians. We aimed to investigate the cytotoxic and apoptotic effects of AT-101 in mouse pituitary corticotroph tumor AtT20 cells. Methods: Cytotoxic effect of AT-101 was assessed by XTT cell viability assay. Apoptosis was shown by measuring DNA fragmentation and Caspase-3/7 activity. Changes in mRNA expressions of apoptosis-related genes were investigated by qPCR array after treatment with AT-101. ACTH was measured by ACTH-EIA Kit. Results: AT-101 induced cytotoxicity and apoptosis in AtT20 cells. mRNA levels of pro-apoptotic genes such as TNFR-SF-10B, Bid, PYCARD, Caspase-8, Caspase-3, and Caspase-7 were induced by 2.0-, 1.5-, 1.7-, 1.5-, 1.6-, and 2-fold, respectively, in AtT20 cells by AT-101 treatment. Moreover, some of the anti-apoptotic genes such as BCL2L10, NAIP1, and PAK-7 were reduced by 2.1-, 2.3-, 4.0-fold, respectively, in AtT20 cells. AT-101 also decreased ACTH secretion significantly. Conclusion: AT-101 induces apoptosis in mouse pituitary corticotroph tumor cells. © 2017, Italian Society of Endocrinology (SIE).
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ACTH-Secreting Pituitary Adenoma , Adenoma , Adrenocorticotropic Hormone , Animals , Antineoplastic Agents, Phytogenic , Apoptosis , Apoptosis Regulatory Proteins , Cell Proliferation , Gossypol , Mice , Pituitary Neoplasms , Tumor Cells, Cultured , caspase 3 , caspase 7 , caspase 8 , DNA , isosorbide , messenger RNA , p21 activated kinase 7 , protein Bid , antineoplastic agent , apoptosis regulatory protein , corticotropin , gossypol , gossypol acetic acid , ACTH secreting cell , animal cell , antiproliferative activity , apoptosis , Article , BCL2L10 gene , Bid gene , caspase 3 gene , caspase 7 gene , caspase 8 gene , cell viability , controlled study , DNA fragmentation , drug cytotoxicity , drug mechanism , drug research , gene , gene expression , hormone inhibition , hormone release , mouse , NAIP1 gene , nonhuman , PAK 7 gene , pituitary tumor cell line , polymerase chain reaction , PYCARD gene , quantitative analysis , TNFR SF 10B gene , ACTH secreting adenoma , adenoma , analogs and derivatives , animal , antagonists and inhibitors , cell proliferation , drug effect , hypophysis tumor , metabolism , pathology , tumor cell culture