Linalool preferentially induces robust apoptosis of a variety of leukemia cells via upregulating p53 and cyclin-dependent kinase inhibitors.
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.
Gu
Ying
Y
Department of Hematology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, China.
Ting
Zhang
Z
Qiu
Xi
X
Zhang
Xuzhao
X
Gan
Xiaoxian
X
Fang
Yongming
Y
Xu
Xiaohua
X
Xu
Rongzhen
R
D000080462:Acyclic Monoterpenes; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors*; D006801:Humans; D039821:Monoterpenes / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects*
D000080462:Acyclic Monoterpenes; D039821:Monoterpenes; D047428:Protein Kinase Inhibitors; D016159:Tumor Suppressor Protein p53; C018584:linalool; D018844:Cyclin-Dependent Kinases