Anti-neoplastic effect of protein kinase CK2 inhibitor, 2-dimethylamino-4,5,6,7-tetrabromobenzimidazole (DMAT), on growth and hormonal activity of human adrenocortical carcinoma cell line (H295R) in vitro |
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Authors: | Hanna Lawnicka Magdalena Kowalewicz-Kulbat Paulina Sicinska Zygmunt Kazimierczuk Pawel Grieb Henryk Stepien |
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Institution: | (1) Department of Immunoendocrinology, 1st Chair of Endocrinology, Medical University of Lodz, Dr. Sterling 3 Street, 91-425 Lodz, Poland;(2) Department of Immunology and Infectious Biology, University of Lodz, Banacha 12/16, 90-237 Lodz, Poland;(3) Department of Molecular Biophysics, University of Lodz, Banacha 12/16, 90-237 Lodz, Poland;(4) Department of Experimental Pharmacology, Mossakowski Medical Research Center, Polish Academy of Sciences, Pawinskiego 5, 02-124 Warsaw, Poland; |
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Abstract: | Several studies indicate the involvement of protein kinases in the progression of various malignancies. Kinase inhibitors
are therefore becoming important anticancer drugs. CK2 kinase (casein kinase-2) has been suggested to be a constituent of
a neoplastic milleu, and its inhibition might represent a new approach to cancer therapy. Adrenocortical carcinomas (ACCs)
are highly malignant neoplasms with poor overall prognosis. We have examined the effects of 2-dimethylamino-4,5,6,7-tetrabromobenzimidazole
(DMAT), a potent CK2 inhibitor, on the H295R human adrenocortical cancer cell line. Treatment with DMAT decreases the secretion
of aldosterone, dehydroepiandrosterone sulfate, and androstendione and results in an accumulation of 17-OH-progesterone. Cell
growth as measured by the MTT and 5-bromo-2′-deoxyuridine incorporation assays is inhibited, and cell cycle analysis has revealed
a slight induction of apoptosis. Thus, CK2 kinase activity is probably involved in human ACC endocrine activity and growth. |
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