casein-kinase-ii and Adrenal-Cortex-Neoplasms

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.

Topics: 17-alpha-Hydroxyprogesterone; Adrenal Cortex Hormones; Adrenal Cortex Neoplasms; Adrenocortical Carcinoma; Aldosterone; Antineoplastic Agents; Benzimidazoles; Casein Kinase II; Cell Cycle; Cell Line, Tumor; Cell Proliferation; Cell Survival; Dehydroepiandrosterone Sulfate; Drug Screening Assays, Antitumor; Humans; Hydrocortisone; Protein Kinase Inhibitors