title: 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.
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.
authors.affiliation: Department of Immunoendocrinology, 1st Chair of Endocrinology, Medical University of Lodz, Dr. Sterling 3 Street, 91-425, Lodz, Poland.
authors.forename: Hanna
authors.initials: H
authors.lastname: Lawnicka
authors.forename: Magdalena
authors.initials: M
authors.lastname: Kowalewicz-Kulbat
authors.forename: Paulina
authors.initials: P
authors.lastname: Sicinska
authors.forename: Zygmunt
authors.initials: Z
authors.lastname: Kazimierczuk
authors.forename: Pawel
authors.initials: P
authors.lastname: Grieb
authors.forename: Henryk
authors.initials: H
authors.lastname: Stepien
mesh_terms: D019326:17-alpha-Hydroxyprogesterone / Q000378:metabolism; D000305:Adrenal Cortex Hormones / Q000378:metabolism*; D000306:Adrenal Cortex Neoplasms / Q000378:metabolism / Q000473:pathology*; D018268:Adrenocortical Carcinoma / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D000450:Aldosterone / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology; D001562:Benzimidazoles / Q000494:pharmacology*; D047390:Casein Kinase II / Q000037:antagonists & inhibitors*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D019314:Dehydroepiandrosterone Sulfate / Q000378:metabolism; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*
chemical_list: C475924:4,5,6,7-tetrabromobenzimidazole; D000305:Adrenal Cortex Hormones; D000970:Antineoplastic Agents; D001562:Benzimidazoles; D047428:Protein Kinase Inhibitors; D000450:Aldosterone; D019314:Dehydroepiandrosterone Sulfate; D019326:17-alpha-Hydroxyprogesterone; D047390:Casein Kinase II; D006854:Hydrocortisone