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Linalool preferentially induces robust apoptosis of a variety of leukemia cells via upregulating p53 and cyclin-dependent kinase inhibitors. 2010

Ying Gu, and Zhang Ting, and Xi Qiu, and Xuzhao Zhang, and Xiaoxian Gan, and Yongming Fang, and Xiaohua Xu, and Rongzhen Xu
Department of Hematology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, China.

Linalool, a natural small molecule monoterpene, has been shown to have anti-tumor activity against several human tumor cell lines in vitro; however, the anti-leukemia spectrum and molecular mechanisms inhibiting tumor cell growth are not fully understood. In the present study, we demonstrated that linalool preferentially induced growth arrest and apoptosis of a variety of human leukemia cells, but spared normal hematopoietic cells. Treatment of leukemia cells by linalool for 12h led to strong activation of p53, cyclin-dependent kinase inhibitors (CDKIs), GADD45alpha, c-jun and phosphorylated-JNK, suggesting that linalool-induced apoptosis might be associated with activation of p53 and CDKIs. The findings here warrant further investigation of this class of natural product as lead compound for developing novel therapeutic agents for leukemia.

UI MeSH Term Description Entries
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000080462 Acyclic Monoterpenes Linear compounds that contain a single monoterpene unit. Monoterpenes, Acyclic
D015854 Up-Regulation A positive regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins. Receptor Up-Regulation,Upregulation,Up-Regulation (Physiology),Up Regulation
D016159 Tumor Suppressor Protein p53 Nuclear phosphoprotein encoded by the p53 gene (GENES, P53) whose normal function is to control CELL PROLIFERATION and APOPTOSIS. A mutant or absent p53 protein has been found in LEUKEMIA; OSTEOSARCOMA; LUNG CANCER; and COLORECTAL CANCER. p53 Tumor Suppressor Protein,Cellular Tumor Antigen p53,Oncoprotein p53,TP53 Protein,TRP53 Protein,p53 Antigen,pp53 Phosphoprotein,Phosphoprotein, pp53
D017209 Apoptosis A regulated cell death mechanism characterized by distinctive morphologic changes in the nucleus and cytoplasm, including the endonucleolytic cleavage of genomic DNA, at regularly spaced, internucleosomal sites, i.e., DNA FRAGMENTATION. It is genetically programmed and serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. Apoptosis, Extrinsic Pathway,Apoptosis, Intrinsic Pathway,Caspase-Dependent Apoptosis,Classic Apoptosis,Classical Apoptosis,Programmed Cell Death,Programmed Cell Death, Type I,Apoptoses, Extrinsic Pathway,Apoptoses, Intrinsic Pathway,Apoptosis, Caspase-Dependent,Apoptosis, Classic,Apoptosis, Classical,Caspase Dependent Apoptosis,Cell Death, Programmed,Classic Apoptoses,Extrinsic Pathway Apoptoses,Extrinsic Pathway Apoptosis,Intrinsic Pathway Apoptoses,Intrinsic Pathway Apoptosis
D045744 Cell Line, Tumor A cell line derived from cultured tumor cells. Tumor Cell Line,Cell Lines, Tumor,Line, Tumor Cell,Lines, Tumor Cell,Tumor Cell Lines
D047428 Protein Kinase Inhibitors Agents that inhibit PROTEIN KINASES. Protein Kinase Inhibitor,Inhibitor, Protein Kinase,Inhibitors, Protein Kinase,Kinase Inhibitor, Protein,Kinase Inhibitors, Protein
D018844 Cyclin-Dependent Kinases Protein kinases that control cell cycle progression in all eukaryotes and require physical association with CYCLINS to achieve full enzymatic activity. Cyclin-dependent kinases are regulated by phosphorylation and dephosphorylation events. Cyclin-Dependent Kinase,Cyclin-Dependent Protein Kinase,cdk Proteins,Cyclin-Dependent Protein Kinases,Cyclin Dependent Kinase,Cyclin Dependent Kinases,Cyclin Dependent Protein Kinase,Cyclin Dependent Protein Kinases,Kinase, Cyclin-Dependent,Kinase, Cyclin-Dependent Protein,Protein Kinase, Cyclin-Dependent
D039821 Monoterpenes Compounds with a core of 10 carbons generally formed via the mevalonate pathway from the combination of 3,3-dimethylallyl pyrophosphate and isopentenyl pyrophosphate. They are cyclized and oxidized in a variety of ways. Due to the low molecular weight many of them exist in the form of essential oils (OILS, VOLATILE). Monoterpene,Monoterpenoid,Monoterpenoids

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