Linalool inhibits the growth of human T cell acute lymphoblastic leukemia cells with involvement of the MAPK signaling pathway

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 T-ALL 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 inhibited the growth of T-ALL 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 T-ALL cells at the G₀/G₁ phase, and induced the apoptosis of T-ALL 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 T-ALL 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 T-ALL cells. In conclusion, the present study revealed that linalool inhibits T-ALL cell survival with involvement of the MAPK signaling pathway. JNK activation and ERK inhibition may play a functional role in apoptosis induction of T-ALL cells. Linalool may be developed as a novel anti T-ALL agent.

Keywords: T cell; leukemia; linalool; mitogen-activated protein kinases.