Effects of Indeno[1,2-b]indol inhibitors of human protein kinase CK2 on different tumor cell lines., Homburg, 6.-9.9.2016.

Aichele D, Pataillot J, Le Borgne M, Jose J

Abstract

Increased protein kinase CK2 activity is involved in many human diseases such as cancer (1). In consequence CK2 is an emerging major target for drug design. Several indeno[1,2-b]indole-9,10-dionederivatives containing N5-isopropyl substitutions on the C-Ring were synthesized and have been reported as potent ATP-competitive CK2 inhibitors (2,3).Here we report on the evaluation of these inhibitors, containing different substituents in the A- and D-ring, for their effects on various tumor cell lines: breast cancer cells MCF-7, lung carcinoma cells A427 andepidermal cancer cell line A431. Antiproliferating effects of selected inhibitors were tested using incorporation of nucleoside analog 5-ethynyl-2`-deoxyuridine during DNA-synthesis (EdU-assay).Treatment of A431 cells with 20 μM indeno[1,2-b]indoles for 24 h caused a moderate decrease of cell proliferation by 30% for all tested compounds. These rather unspecific effects were also seen for A427cells. In contrast effects of inhibitors on the proliferation rates of MCF7 cells seem to be dependent on the structure of the compounds. Best results were obtained with compound 3 . The total cell number wasreduced by 90% after 24 h. Most of the remaining cells exhibited apoptotic morphology and showed nearly none proliferating activity. This study shows that potent CK2 inhibitors as tested can exhibit distincteffects on different tumor cell lines. Among those compound 3 appears to be an antiproliferating agent with high activity toward MCF7 cells.