Protein kinase CK2 inhibition is associated with the destabilization of HIF-1α in human cancer cells
B Guerra, TDL Rasmussen, A Schnitzler, HH Jensen… - Cancer Letters, 2015 - Elsevier
B Guerra, TDL Rasmussen, A Schnitzler, HH Jensen, BS Boldyreff, Y Miyata, N Marcussen…
Cancer Letters, 2015•ElsevierScreening for protein kinase CK2 inhibitors of the structural diversity compound library (DTP
NCI/NIH) led to the discovery of 4-[(E)-(fluoren-9-ylidenehydrazinylidene)-methyl] benzoic
acid (E9). E9 induces apoptotic cell death in various cancer cell lines and upon hypoxia, the
compound suppresses CK2-catalyzed HSP90/Cdc37 phosphorylation and induces HIF-1α
degradation. Furthermore, E9 exerts a strong anti-tumour activity by inducing necrosis in
murine xenograft models underlining its potential to be used for cancer treatment in future …
NCI/NIH) led to the discovery of 4-[(E)-(fluoren-9-ylidenehydrazinylidene)-methyl] benzoic
acid (E9). E9 induces apoptotic cell death in various cancer cell lines and upon hypoxia, the
compound suppresses CK2-catalyzed HSP90/Cdc37 phosphorylation and induces HIF-1α
degradation. Furthermore, E9 exerts a strong anti-tumour activity by inducing necrosis in
murine xenograft models underlining its potential to be used for cancer treatment in future …
Abstract
Screening for protein kinase CK2 inhibitors of the structural diversity compound library (DTP NCI/NIH) led to the discovery of 4-[(E)-(fluoren-9-ylidenehydrazinylidene)-methyl]benzoic acid (E9).
E9 induces apoptotic cell death in various cancer cell lines and upon hypoxia, the compound suppresses CK2-catalyzed HSP90/Cdc37 phosphorylation and induces HIF-1α degradation.
Furthermore, E9 exerts a strong anti-tumour activity by inducing necrosis in murine xenograft models underlining its potential to be used for cancer treatment in future clinical studies.
Crystal structure analysis of human and maize CK2α in complex with E9 reveals unique binding properties of the inhibitor to the enzyme, accounting for its affinity and selectivity.
Elsevier