Synergistic Interactions of 5-Fluorouracil with Inhibitors of Protein Kinase CK2 Correlate with p38 MAPK Activation and FAK Inhibition in the Triple-Negative Breast Cancer Cell Line

Patrycja Wińska; Olena Karatsai; Monika Staniszewska; Mirosława Koronkiewicz; Konrad Chojnacki; Maria Jolanta Rędowicz

doi:10.3390/ijms21176234

August 28, 2020International Journal of Molecular SciencesOpen Access

Synergistic Interactions of 5-Fluorouracil with Inhibitors of Protein Kinase CK2 Correlate with p38 MAPK Activation and FAK Inhibition in the Triple-Negative Breast Cancer Cell Line

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Key Points

Investigate the combined anticancer effects of 5-fluorouracil and protein kinase CK2 inhibitors on triple-negative and hormone receptor-positive breast cancer cell lines.
Determined cell viability and synergy metrics using MTT assays and the Chou-Talalay combination index (CI) model in MDA-MB-231 and MCF-7 cell lines.
Assessed cell cycle dynamics, apoptosis markers, and the activation of FAK, p38 MAPK, and ERK1/2 via flow cytometry and western blotting in MDA-MB-231 cells.
Visualized the cellular actin filament network using confocal microscopy following combination drug exposure.
Combined treatment of 5-FU with CK2 inhibitors (14B or CX-4945) exhibited synergistic cytotoxicity (CI < 1) in MDA-MB-231 cells, while 5-FU with 14B showed an antagonistic effect in MCF-7 cells.
Synergistic cell death in MDA-MB-231 cells correlated with p38 MAPK activation, FAK inhibition, upregulated pro-apoptotic markers, S-phase cell cycle delay, and disruption of the actin cytoskeleton.

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Implication

In vitro study uncovers synergistic cytotoxicity of 5-fluorouracil and CK2 inhibitors in triple-negative breast cancer cells, indicating potential targets to enhance chemotherapy.

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Wińska et al. (2020) studied this question.

synapsesocial.com/papers/6aadda730e0d4884f9873d8d https://doi.org/10.3390/ijms21176234

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Synergistic Interactions of 5-Fluorouracil with Inhibitors of Protein Kinase CK2 Correlate with p38 MAPK Activation and FAK Inhibition in the Triple-Negative Breast Cancer Cell Line

Key Points

No abstract yet

Implication

Discussion

Cite This Study

Synergistic Interactions of 5-Fluorouracil with Inhibitors of Protein Kinase CK2 Correlate with p38 MAPK Activation and FAK Inhibition in the Triple-Negative Breast Cancer Cell Line

Key Points

No abstract yet

Implication

Discussion

Cite This Study

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