Synergistic therapeutic effect of diethylstilbestrol and CX-4945 in human acute T-lymphocytic leukemia cells

Jung, Jung-Il; Park, Kyeong‐Yong; Kim, Soon Ae; Kim, Jiyeon

doi:10.1016/j.biopha.2017.12.078

Cited by 6 publications

(4 citation statements)

References 40 publications

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“…Additionally, it was demonstrated that bortezomib (proteasome inhibitor)/CX-4945 combined treatment induced synergistic apoptotic effects in T-and B-ALL cell lines, via reduction of chaperoning activity of Hsp90 (9) and inhibition of NF-ĸB signaling in T-ALL cell lines as well as in primary cells from T-ALL patients. Recently, it has also been shown that T-ALL cells express high levels of CK2 subunits, and that CK2 inhibition by CX-4945 had synergistic effects promoting the inhibition of survival and IL-2 production in T-ALL cells (10). Other studies demonstrated that simultaneous treatment of A2780 and SKOV-3 ovarian cancer cells with CX-4945 and cisplatin or gemcitabine promotes synergistic induction of apoptosis.…”

mentioning

confidence: 99%

Effect of Simultaneous Inhibition of Protein Kinase CK2 and Thymidylate Synthase in Leukemia and Breast Cancer Cells

et al. 2018

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confidence: 99%

Effect of Simultaneous Inhibition of Protein Kinase CK2 and Thymidylate Synthase in Leukemia and Breast Cancer Cells

et al. 2018

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“…We performed viability assays using all inhibitors separately and also using CX-4945 in combination with each TKI. Based on literature 37,38 and our own preliminary experience (Supplementary Figure S5), 10 µM CX-4945 was used in all subsequent experiments (unless indicated otherwise).…”

Section: Effects Of Ck-2 Inhibition In CML Cellsmentioning

confidence: 99%

Inhibition of Casein Kinase 2 induces cell death in chronic myelogenous leukemia cells resistant to tyrosine kinase inhibitors

Mitrovský

Myslivcová

Macháčková-Lopotová

et al. 2021

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Chronic myelogenous leukemia (CML) is a myeloproliferative disease characterized by the presence of a BCR-ABL oncogene. Despite the high performance of treatment with tyrosine kinase inhibitors (TKI), about 30 % of patients develop resistance to therapy. To improve the outcome of CML therapy, the identification of new targets of treatment is needed. Here, we explored the Casein Kinase 2 (CK2) as a potential target for CML therapy. Previously, we detected increased phosphorylation of HSP90β Serine 226 in patients non-responding to TKIs imatinib and dasatinib. This site is known to be phosphorylated among others by CK2, which was also previously linked to CML resistance to imatinib. In the present work, we established six novel imatinib- and dasatinib-resistant CML cell lines and detected increased CK2 activation in all these resistant cells. A CK2 inhibitor, CX-4945, induced cell death of CML cells in both parental and resistant cell lines. In some cases, CK2 inhibition also potentiated the effects of TKI on cell metabolic activity. No effects of CK2 inhibition were observed in normal mononuclear blood cells from healthy donors and BCR-ABL negative HL60 cell line. Our data indicate that CK2 kinase supports CML cell viability even in cells with different mechanisms of resistance to TKI, and thus represents a potential target for treatment.

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“…Several CK2 inhibitors, such as CX‐4945 (Silmitasertib) 6 or CIGB‐300, a novel proapoptotic peptide, 7 entered already the clinical trials phase. CK2 inhibitors could exhibit various synergistic effects with dihydrofolate reductase inhibitors (methotrexate), 8 thymidylate synthase inhibitors (5‐fluorouracil), 9 proteasome inhibitors (bortezomib), 10,11 hypermethylation agents affected epigenetic modulation (decitabine), 12 and other classes of anticancer compounds 13–15 …”

Section: Introductionmentioning

confidence: 99%

The halogenation of natural flavonoids, baicalein and chrysin, enhances their affinity to human protein kinase CK2

et al. 2020

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A series of halogenated derivatives of natural flavonoids: baicalein and chrysin were designed and investigated as possible ligands for the catalytic subunit of tumor-associated human kinase CK2. Thermal shift assay method, in silico modeling, and high-performance liquid chromatography-derived hydrophobicity together with IC 50 values determined in biochemical assay were used to explain the ligand affinity to the catalytic subunit of human protein kinase CK2. Obtained results revealed that substitution of baicalein and chrysin with halogen atom increases their binding affinity to hCK2α, and for 8-chlorochrysin the observed effect is even stronger than for the reference CK2 inhibitor-4,5,6,7-tetrabromo-1H-benzotriazole. The cytotoxic activities of the baicalein and chrysin derivatives in the in vitro model have been evaluated for MV4-11 (human biphenotypic B myelomonocytic leukemia), A549 (human lung adenocarcinoma), LoVo (human colon cancer), and MCF-7 (human breast cancer) as well as on the nontumorigenic human breast epithelial MCF-10A cell lines. Among the baicalein derivatives, the strongest cytotoxic effect was observed for 8-bromobaicalein, which exhibited the highest activity against breast cancer cell line MCF-7 (IC 50 10 ± 3 μM). In the chrysin series, the strongest cytotoxic effect was observed for unsubstituted chrysin, which exhibited the highest activity against leukemic cell line MV4-11 (IC 50 10 ± 4 μM). K E Y W O R D Sbaicalein, chromatographic hydrophobicity index, chrysin, CK2 kinase inhibition, cytotoxic effect, flavonoids, thermal shift assay Abbreviations: BSA, bovine serum albumin; DFT, discrete Fourier transform; DMSO, dimethyl sulfoxide; DSF, differential scanning fluorimetry; gHSQC, gradient heteronuclear single quantum correlation; hCK2α, catalytic subunit of human protein kinase CK2; MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide;

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Synergistic therapeutic effect of diethylstilbestrol and CX-4945 in human acute T-lymphocytic leukemia cells

Cited by 6 publications

References 40 publications

Effect of Simultaneous Inhibition of Protein Kinase CK2 and Thymidylate Synthase in Leukemia and Breast Cancer Cells

Effect of Simultaneous Inhibition of Protein Kinase CK2 and Thymidylate Synthase in Leukemia and Breast Cancer Cells

Inhibition of Casein Kinase 2 induces cell death in chronic myelogenous leukemia cells resistant to tyrosine kinase inhibitors

The halogenation of natural flavonoids, baicalein and chrysin, enhances their affinity to human protein kinase CK2

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