Regulation of cancer progression by CK2: an emerging therapeutic target

Hussain, Shakeel; Guo, Yilei; Huo, Yu; Shi, Juanjuan; Hou, Yongzhong

doi:10.1007/s12032-024-02316-6

Med Oncol

2024

DOI: 10.1007/s12032-024-02316-6

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Regulation of cancer progression by CK2: an emerging therapeutic target

Shakeel Hussain,

Yilei Guo,

Yu Huo

et al.

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2024

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Cited by 2 publications

References 83 publications

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PPARδ Antagonist Inhibited CD47 Expression and Phagocytosis

Guo,

Khan,

Shi

et al. 2024

J of Cellular Biochemistry

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Increasing evidence suggests that CD47 is highly expressed in multiple types of cancer, which could bind to SIRPα on macrophage, leading to inhibition of macrophage phagocytosis and promotion of tumor growth. However, the regulatory mechanism of CD47 gene expression is not completely clear. Our results indicated that colon cancer cells treated with GSK0660 drug, which is one of the PPARδ antagonists, significantly reduced CD47 gene and protein expression levels in a time and dose‐dependent manner. CD47 reporter plasmid was constructed and dual‐luciferase analysis was performed. The results suggest that GSK0660 treatment markedly reduced CD47 gene transcriptional activity. Moreover, co‐cultured analysis showed that GSK0660 treatment increased phagocytosis. BALB/C mice implanted with CT‐26 colon cancer cells were treated with GSK0660, and the results showed that GSK0660 significantly inhibited tumor growth. Moreover, the combination of CD47 monoclonal antibody with GSK0660 drug significantly inhibited tumor growth compared to GSK0660 or CD47 antibody treatment alone. These findings suggest that GSK0660 synergized with CD47 antibody to enhance antitumor immunotherapy.

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PPARδ Antagonist Inhibited CD47 Expression and Phagocytosis

Guo,

Khan,

Shi

et al. 2024

J of Cellular Biochemistry

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Preclinical activity of resazurin in acute myeloid leukaemia

Ha,

Andresen,

Erikstein

et al. 2024

Br J Haematol

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SummaryResazurin, a phenoxazine used in cell viability assays, acts in vitro as an anti‐leukaemic compound through the production of cellular reactive oxygen species (ROS) resulting in mitochondrial dysfunction and cell death. However, the in vivo tolerance and efficacy of resazurin in cancer are unknown. In this study, we investigated the in vitro and in vivo effects of resazurin in acute myeloid leukaemia (AML). Resazurininduced cell death in a dose‐dependent manner in AML cell lines and reduced proliferation and colony formation in ex vivo treated patient‐derived AML cells. Cells treated with a reduced dose of resazurin for 72 h acquired a more mature immunophenotype suggesting cell differentiation as a mechanism contributing to the anti‐leukaemic effect. In vivo optical imaging in healthy mice demonstrated a reduction of resazurin to resorufin within 30 min and non‐detectable after 2 h, supporting dosing twice daily as optimal. In subcutaneous and orthotopic models of MV4‐11 AML in NOD/SCID IL2rγnull mice, anti‐tumour effects and an increased survival were found at a dose level of 75 mg/kg twice daily without observed toxicity. Our results suggest that resazurin represents a novel experimental therapeutic for the treatment of AML.

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Regulation of cancer progression by CK2: an emerging therapeutic target

Cited by 2 publications

References 83 publications

PPARδ Antagonist Inhibited CD47 Expression and Phagocytosis

PPARδ Antagonist Inhibited CD47 Expression and Phagocytosis

Preclinical activity of resazurin in acute myeloid leukaemia

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