No abstract

Linalool can inhibit the malignant proliferation of numerous human malignant solid tumors, including hepatocellular carcinoma, breast cancer, small cell carcinoma and malignant melanoma. However, the role of linalool in T cell acute lymphoblastic leukaemia (T-ALL) remains unclear. In the present study, human TALL cell lines (Jurkat, H9, Molt-4 and Raji cells) and peripheral blood mononuclear cells (PBMCs) from healthy donors were treated with various concentrations of linalool (3.75, 7.50, 15.00, 30.00, 60.00 and 120.00 µM, respectively). A CCK-8 assay was used to analyse cell viability and it demonstrated that linalool inhib ited the growth of TALL cells in a dose-dependent manner, but did not significantly affect normal PBMCs. Flow cytometry was used to detect the cell cycle and apoptosis and demonstrated that linalool reduced the percentage of TALL cells at the G 0 /G 1 phase, and induced the apoptosis of TALL cells. RNA sequencing was conducted on an Illumina HiSeq X Series 2500 before and after treatment with linalool followed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis. It was demonstrated that the mitogen-activated protein kinase (MAPK) pathway was involved in the effect of linalool on TALL cells. Real-time quantitative PCR and western blotting were performed to verify the mRNA and protein levels, respectively of the genes in the signaling pathway identified. In addition, it was found that linalool significantly inhibited phosphorylated (p)-ERK1/2 protein expression and enhanced p-JNK protein expression of TALL cells. In conclusion, the present study revealed that linalool inhibits TALL cell survival with involvement of the MAPK signaling pathway. JNK activation and ERK inhibition may play a functional role in apoptosis induction of TALL cells. Linalool may be developed as a novel anti TALL agent.