It is involved in several cellular processes, such as cell cycle, gene expression, protein synthesis, signal transduction and metabolism; however, its hall-mark is considered its prosurvival and anti-apoptotic function. This is supported by the reduction of CK2 activity or expression is invariantly followed by cell death, mainly due to apoptosis. Consistent with the anti-apoptotic function of CK2, cancer cells, which are characterized by rapid proliferation and defective apoptosis, express particularly high levels of CK2. It has a special role in tumorigenesis, potentiating pathways that are frequently up-regulated or untimely activated in cancer, and it has consequently been defined as “a key player in cancer biology”. Whenever comparison has been performed, CK2 has been shown significantly more abundant in tumor cells than in healthy counterparts. However, at the same time tumors rely more on CK2 for their survival, and this phenomenon, described as “addiction” to CK2 of cancer cells, explains why they are more SCH727965 msds sensitive to its inhibition or knocking-down, compared to normal cells. On these bases, CK2 is presently considered a promising therapeutic target, also exploiting the fact that, due to the peculiar structure of the CK2 catalytic site, several very specific 
inhibitors are available. Many of them have already proved to be able to kill cancer cells and in some cases also employed for successful animal treatment. Apoptosis resistance is a major reason of cancer therapy failure; its mechanisms can be different and multifaceted, and is only partially understood. In many cases it is due to the expression of extrusion pumps of the ABC-transporter family, such as Pgp, which drive drugs outside the cell and reduce their effective concentration. Cells expressing these pumps are selected for their survival in response to treatment with a certain drug, but usually a cross-resistance occurs towards other compounds, even not structurally related; in these cases, cells are indicated as multidrug-resistant. Many other mechanisms have been reported to be involved in apoptosis resistance, including alteration in genetic INCB18424 JAK inhibitor features, DNA repair, drug target molecules, metabolic and growth pathways. In some cases, specific resistance is observed, such as that towards Imatinib and its derivatives targeting Bcr-Abl tyrosine kinase, frequently due to kinase mutations, but also to epigenetic changes, alternative splicing or induction of compensatory signaling pathways. CK2 has been already associated to the phenomenon of drug resistance: it phosphorylates Pgp and another extrusion pump, MRP1 and its inhibition allows a higher accumulation of drugs in Pgp or MRP1 expressing cells, suggesting that CK2 can up-regulate the Pgp function. Moreover, we have previously found that the CK2 catalytic subunit is overexpressed in a MDR cell line compared to the non-MDR counterpart, and that its overexpression contributes to the maintenance of the resistant phenotype. Here we evaluate the efficacy of the CK2 inhibitors CX-4945 and CX-5011 in a number of different cell lines, available as pairs, each pair containing a variant selected for resistance to druginduced apoptosis, and we demonstrate that these compounds can overcome the problem of drug resistance. We first measured CK2 activity in cells treated for different times with increasing concentrations of the compounds.