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.
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.
Lawnicka
Hanna
H
Department of Immunoendocrinology, 1st Chair of Endocrinology, Medical University of Lodz, Dr. Sterling 3 Street, 91-425, Lodz, Poland.
Kowalewicz-Kulbat
Magdalena
M
Sicinska
Paulina
P
Kazimierczuk
Zygmunt
Z
Grieb
Pawel
P
Stepien
Henryk
H
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*
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