title: Linalool Induces Cell Cycle Arrest and Apoptosis in Leukemia Cells and Cervical Cancer Cells through CDKIs.
abstract: Plantaginaceae, a popular traditional Chinese medicine, has long been used for treating various diseases from common cold to cancer. Linalool is one of the biologically active compounds that can be isolated from Plantaginaceae. Most of the commonly used cytotoxic anticancer drugs have been shown to induce apoptosis in susceptible tumor cells. However, the signaling pathway for apoptosis remains undefined. In this study, the cytotoxic effect of linalool on human cancer cell lines was investigated. Water-soluble tetrazolium salts (WST-1) based colorimetric cellular cytotoxicity assay, was used to test the cytotoxic ability of linalool against U937 and HeLa cells, and flow cytometry (FCM) and genechip analysis were used to investigate the possible mechanism of apoptosis. These results demonstrated that linalool exhibited a good cytotoxic effect on U937 and HeLa cells, with the IC50 value of 2.59 and 11.02 μM, respectively, compared with 5-FU with values of 4.86 and 12.31 μM, respectively. After treating U937 cells with linalool for 6 h, we found an increased sub-G1 peak and a dose-dependent phenomenon, whereby these cells were arrested at the G0/G1 phase. Furthermore, by using genechip analysis, we observed that linalool can promote p53, p21, p27, p16, and p18 gene expression. Therefore, this study verified that linalool can arrest the cell cycle of U937 cells at the G0/G1 phase and can arrest the cell cycle of HeLa cells at the G2/M phase. Its mechanism facilitates the expression of the cyclin-dependent kinases inhibitors (CDKIs) p53, p21, p27, p16, and p18, as well as the non-expression of cyclin-dependent kinases (CDKs) activity.
authors.affiliation: Department of Medical Laboratory Science and Biotechnology, School of Medical and Health Sciences, Fooyin University, Ta-Liao District, Kaohsiung 83102, Taiwan. ft049@fy.edu.tw.
authors.forename: Mei-Yin
authors.initials: MY
authors.lastname: Chang
authors.affiliation: Department of Biotechnology, Collage of Pharmacy and Health Care, Tajen University, Yanpu Township, Pingtung County 90741, Taiwan. deshieh@tajen.edu.tw.
authors.forename: Den-En
authors.initials: DE
authors.lastname: Shieh
authors.affiliation: Department of Medical Laboratory Science and Biotechnology, School of Medical and Health Sciences, Fooyin University, Ta-Liao District, Kaohsiung 83102, Taiwan. ft050@fy.edu.tw.
authors.forename: Chung-Chi
authors.initials: CC
authors.lastname: Chen
authors.affiliation: Department of Nutrition and Health Science, School of Medical and Health Sciences, Fooyin University, Ta-Liao District, Kaohsiung 83102, Taiwan. janson.yeh@msa.hinet.net.
authors.forename: Ching-Sheng
authors.initials: CS
authors.lastname: Yeh
authors.affiliation: Department of Physical Therapy, School of Medical and Health Sciences, Fooyin University, Ta-Liao District, Kaohsiung 83102, Taiwan. mt067@fy.edu.tw.
authors.forename: Huei-Ping
authors.initials: HP
authors.lastname: Dong
mesh_terms: D000080462:Acyclic Monoterpenes; D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects*; D050756:Cyclin-Dependent Kinase Inhibitor Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006367:HeLa Cells; D006801:Humans; D007938:Leukemia / Q000378:metabolism*; D039821:Monoterpenes / Q000633:toxicity*; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D002583:Uterine Cervical Neoplasms / Q000378:metabolism*
chemical_list: D000080462:Acyclic Monoterpenes; D050756:Cyclin-Dependent Kinase Inhibitor Proteins; D039821:Monoterpenes; D015513:Oncogene Proteins; D016159:Tumor Suppressor Protein p53; C018584:linalool
keywords: apoptosis; cyclin-dependent kinases (CDKs); cyclin-dependent kinases inhibitors (CDKIs); flow cytometry (FCM); genechip; linalool