Abstract
PURPOSE: Vitamin K1 (VK1) has been proved to have anticancer properties in various cancer cells. However, little is known about the effects of VK1 on hematologic malignancies. The aim of this study was to evaluate the cytotoxic effects of VK1 on Jurkat T Lymphocyte Leukemia Cells (Jurkat T cells), as well as to investigate the changes in gene expression. METHODS: Jurkat T cells and normal human peripheral blood mononuclear cells (PBMCs) were treated with VK1 at different concentrations, and the cell viabilities were evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cell apoptosis was detected by Annexin V-FITC cell apoptosis detection kit and the cell cycle was determined by PI staining and flow cytometric analysis. Differentially expressed genes (DEGs) of Jurkat T cells induced by VK1 were analyzed by RNA sequencing. The mRNA expression of HMGCR and HMGCS1 were further verified by real-time RT-qPCR. RESULTS: VK1 showed an obviously antiproliferative effect on Jurkat T cells but no any effects on normal human PBMCs. VK1 induced Jurkat T cells apoptosis and cell cycle arrest at G0/G1 phase. A total of 21 down-regulated and 34 up-regulated genes were identified by transcriptome analysis. We selected HMGCR and HMGCS1 genes among the significantly up-regulated genes for further RT-qPCR analyzation. It was confirmed that VK1 up-regulated the mRNA expression of HMGCR and HMGCS1. CONCLUSION: VK1 has cytotoxic effects and transcriptional regulation of multiple genes on Jurkat T cells. The genes of HMGCR and HMGCS1 related pathways may play roles in this process.