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

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.

[Retracted] Linalool Impress Colorectal Cancer Deterioration by Mediating AKT/mTOR and JAK2/STAT3 Signaling Pathways

“…Previous studies based on other cancer species also reveal the effect of linalool on cell signaling pathways. Studies show that linalool can inhibit glioma cells by regulating SIRT3-SOD2-ROS signaling [ 25 ]. In addition, linalool also inhibits the survival of T-ALL cells through the MAPK pathway, and JNK activation and ERK inhibition may play a functional role in the induction of apoptosis of T-ALL cells.…”

Linalool Induces Reactive Oxygen Species Mediated Apoptosis in Human Oral Squamous Carcinoma Cells

“…were also mediated by linalool to exhibit its antitumor action [16] . Gong et al verified by morphological analysis that linalool inhibits the viability of Jurkat cells via inducing the apoptosis of leukemia cells [17] . Linalool treatment exhibited fragmentation of chromatin, bleb formation on the cell surface, cytoplasmic shrinkage, loss of cell-to-cell contact and a reduction in their density, which is representative apoptotic features.…”

Immunomodulatory Role of Rosmarinus officinalis L., Mentha x piperita L., and Lavandula angustifolia L. Essential Oils in Sheep Peripheral Blood Mononuclear Cells

“…No studies were available on the blastogenic responses of EOs in sheep in an in vitro model of inflammation. Recent research mainly reported the anti-proliferative effects of linalool, one of the main chemical active compounds in LEO [50], L. angustifolia [51], R. officinalis [52], and M. x piperita Eos [53], on different tumor-derived cell lines. Very few findings reported the effects of EOs on peripheral blood leukocytes' proliferation in humans.…”