Diffuse Large B-cell Lymphoma (DLBCL) accounts for approximately 35% of non-Hodgkin lymphomas in adult patients. While most cases are curable with chemotherapy, a significant subset either fails to respond or eventually relapses. This highlights the need for new therapeutic targets to improve treatment outcomes. Protein kinase CK2, a Ser/Thr kinase expressed in all eukaryotic cells, is overexpressed in DLBCL and other hematological malignancies. CK2 plays a key role in regulating pathways related to cell survival and proliferation, and its inhibition has been shown to induce cytotoxicity in DLBCL. SGC-CK2-1 is a novel and selective CK2 inhibitor that has not yet reached clinical trial phases but demonstrates “in vitro” improved specificity compared to other inhibitors. In this study, we tested the effect of SGC-CK2-1 in DLBCL cells, by evaluating its dose-dependent cytotoxic effects on two germinal center- derived DLBCL cell lines, OCI-LY 1 and OCI-LY 19. Treatment led to a significant decrease in viable cell numbers, primarily due to increased apoptosis, as indicated by elevated Sub-G1 phase populations in cell cycle analysis and increased percentage of Annexin V positive cells. Expression of anti-apoptotic members of the BCL-2 family proteins were reduced in OCI-LY 1 cells, while in OCI-LY 19, only MCL-1 showed a similar response. Both cell lines exhibited reduced phosphorylation of AKT at Ser129 as main target of CK2 and at the activating site Ser473 confirming effective CK2 inhibition by SGC-CK2-1. These results suggest that this novel CK2 inhibitor promotes apoptosis in DLBCL cell lines and may offer a promising new therapeutic strategy for DLBCL.
Diffuse Large B-cell Lymphoma (DLBCL) accounts for approximately 35% of non-Hodgkin lymphomas in adult patients. While most cases are curable with chemotherapy, a significant subset either fails to respond or eventually relapses. This highlights the need for new therapeutic targets to improve treatment outcomes. Protein kinase CK2, a Ser/Thr kinase expressed in all eukaryotic cells, is overexpressed in DLBCL and other hematological malignancies. CK2 plays a key role in regulating pathways related to cell survival and proliferation, and its inhibition has been shown to induce cytotoxicity in DLBCL. SGC-CK2-1 is a novel and selective CK2 inhibitor that has not yet reached clinical trial phases but demonstrates “in vitro” improved specificity compared to other inhibitors. In this study, we tested the effect of SGC-CK2-1 in DLBCL cells, by evaluating its dose-dependent cytotoxic effects on two germinal center- derived DLBCL cell lines, OCI-LY 1 and OCI-LY 19. Treatment led to a significant decrease in viable cell numbers, primarily due to increased apoptosis, as indicated by elevated Sub-G1 phase populations in cell cycle analysis and increased percentage of Annexin V positive cells. Expression of anti-apoptotic members of the BCL-2 family proteins were reduced in OCI-LY 1 cells, while in OCI-LY 19, only MCL-1 showed a similar response. Both cell lines exhibited reduced phosphorylation of AKT at Ser129 as main target of CK2 and at the activating site Ser473 confirming effective CK2 inhibition by SGC-CK2-1. These results suggest that this novel CK2 inhibitor promotes apoptosis in DLBCL cell lines and may offer a promising new therapeutic strategy for DLBCL.
TESTING THE NOVEL PROTEIN KINASE CK2 INHIBITOR SGC-CK2-1, IN DIFFUSE LARGE B CELL LYMPHOMA CELLS
PARADISO, LEONARDO
2024/2025
Abstract
Diffuse Large B-cell Lymphoma (DLBCL) accounts for approximately 35% of non-Hodgkin lymphomas in adult patients. While most cases are curable with chemotherapy, a significant subset either fails to respond or eventually relapses. This highlights the need for new therapeutic targets to improve treatment outcomes. Protein kinase CK2, a Ser/Thr kinase expressed in all eukaryotic cells, is overexpressed in DLBCL and other hematological malignancies. CK2 plays a key role in regulating pathways related to cell survival and proliferation, and its inhibition has been shown to induce cytotoxicity in DLBCL. SGC-CK2-1 is a novel and selective CK2 inhibitor that has not yet reached clinical trial phases but demonstrates “in vitro” improved specificity compared to other inhibitors. In this study, we tested the effect of SGC-CK2-1 in DLBCL cells, by evaluating its dose-dependent cytotoxic effects on two germinal center- derived DLBCL cell lines, OCI-LY 1 and OCI-LY 19. Treatment led to a significant decrease in viable cell numbers, primarily due to increased apoptosis, as indicated by elevated Sub-G1 phase populations in cell cycle analysis and increased percentage of Annexin V positive cells. Expression of anti-apoptotic members of the BCL-2 family proteins were reduced in OCI-LY 1 cells, while in OCI-LY 19, only MCL-1 showed a similar response. Both cell lines exhibited reduced phosphorylation of AKT at Ser129 as main target of CK2 and at the activating site Ser473 confirming effective CK2 inhibition by SGC-CK2-1. These results suggest that this novel CK2 inhibitor promotes apoptosis in DLBCL cell lines and may offer a promising new therapeutic strategy for DLBCL.| File | Dimensione | Formato | |
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https://hdl.handle.net/20.500.12608/89740