Context and objective: The production of ceramide-1-phosphate, which is catalysed by ceramide kinase (CerK), may influence a number of cellular processes, including inflammation and cell division. Here, we looked at how the newly created CerK inhibitor NVP-231 affected the viability and proliferation of cancer cells, as well as the function of cell cycle regulators linked to these reactions.
Experimental methodology: Gradually increasing concentrations of NVP-231 were applied to the lung cancer cell line NCI-H358 and the breast cancer cell line MCF-7 in order to measure DNA synthesis, colony formation, and cell death. The cell cycle distribution of the cells was analyzed using flow cytometry, and alterations in the expression and activation of cell cycle regulators were found using Western blot analysis.
Important findings: NVP-231 decreased DNA synthesis, colony formation, and cell survival in both cell lines in a concentration-dependent manner. Additionally, it caused apoptosis, as seen by elevated caspase-3 and caspase-9 cleavage and DNA fragmentation. NVP-231 reduced the proportion of cells in the S phase and caused an M phase arrest with an elevated mitotic index, as shown by increased histone H3 phosphorylation, according to cell cycle analysis. When staurosporine was added to NVP-231 therapy, the impact on the cell cycle became even more noticeable. Lastly, siRNA-induced down-regulation of CerK sensitized cells to staurosporine-induced apoptosis, although overexpression of CerK protected against this process.
Conclusions and significance: our findings reveal for the first time the critical function that CerK plays in the regulation of the M phase in cancer cells. We propose that CerK be specifically inhibited, with the use of medications like NVP-231, in conjunction with standard pro-apoptotic treatment.
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Journal of Surgery received 288 citations as per Google Scholar report
