DMAT, an inhibitor of protein kinase CK2 induces reactive oxygen species and DNA double strand breaks.
Elevated levels of protein kinase CK2 were found in tumour cells compared to normal cells. Thus, inhibition of CK2 kinase activity seems to be an attractive method to stop growth of cancer cells. Two drugs, namely tetrabromobenzotriazole, TBB, and 2-dimethylamino-4,5,6,7-tetrabromo-1H-benzimidazole, DMAT were found to specifically inhibit CK2 and to induce apoptosis in tumour cells. The aim of the present study was the elucidation of the mode of action of these two inhibitors in addition to the inhibition of CK2 activity. The decrease in CK2 kinase activity induced by both inhibitors was accompanied by a reduction in cell viability and induction of apoptosis. Most interestingly, we detected that DMAT in contrast to TBB induced reactive oxygen species, ROS and DNA-double-strand-breaks (DSBs). Thus, in addition to inhibition of CK2 one has to consider ROS and DSBs contributing to the induction of apoptosis by DMAT.
Medizinische Biochemie und Molekularbiologie, Universität des Saarlandes, 66424 Homburg, Germany.
Carolin C
CC
Schneider
Andrea
A
Hessenauer
Claudia
C
Götz
Mathias
M
Montenarh
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001562:Benzimidazoles / Q000494:pharmacology*; D047390:Casein Kinase II / Q000037:antagonists & inhibitors* / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D053903:DNA Breaks, Double-Stranded; D006801:Humans; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects*; D011471:Prostatic Neoplasms / Q000201:enzymology* / Q000235:genetics; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013997:Time Factors; D014230:Triazoles / Q000494:pharmacology; D015854:Up-Regulation
C492322:2-dimethylamino-4,5,6,7-tetrabromo-1H-benzimidazole; C405354:4,5,6,7-tetrabromobenzotriazole; D000970:Antineoplastic Agents; D001562:Benzimidazoles; D047428:Protein Kinase Inhibitors; D017382:Reactive Oxygen Species; D014230:Triazoles; D047390:Casein Kinase II