title: Alpha-phellandrene-induced apoptosis in mice leukemia WEHI-3 cells in vitro.
abstract: Although reports have shown that α-phellandrene (α-PA) is one of the monoterpenes and is often used in the food and perfume industry, our previous studies have indicated that α-PA promoted immune responses in normal mice in vivo. However, there is no available information to show that α-PA induced cell apoptosis in cancer cells, thus, we investigated the effects of α-PA on the cell morphology, viability, cell cycle distribution, and apoptosis in mice leukemia WEHI-3 cells in vitro. Results indicated that α-PA induced cell morphological changes and decreased viability, induced G0/G1 arrest and sub-G1 phase (apoptosis) in WEHI-3 cells. α-PA increased the productions of reactive oxygen species (ROS) and Ca2+and decreased the levels of mitochondrial membrane potential (ΔΨm) in dose- and time-dependent manners in WEHI-3 cells that were analyzed by flow cytometer. Results from confocal laser microscopic system examinations show that α-PA promoted the release of cytochrome c, AIF, and Endo G from mitochondria in WEHI-3 cells. These results are the first findings to provide new information for understanding the mechanisms by which α-PA induces cell cycle arrest and apoptosis in WEHI-3 cells in vitro. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1640-1651, 2016.
authors.affiliation: Graduate Institute of Chinese Medicine, China Medical University, Taichung, 404, Taiwan.|Division of Cardiology, China Medical University Hospital, Taichung, 404, Taiwan.
authors.forename: Jen-Jyh
authors.initials: JJ
authors.lastname: Lin
authors.affiliation: Department of Biological Science and Technology, China Medical University, Taichung, 404, Taiwan.
authors.forename: Shu-Chun
authors.initials: SC
authors.lastname: Hsu
authors.affiliation: College of Chinese Medicine, School of Post-Baccalaureate Chinese Medicine, China Medical University, Taichung, 404, Taiwan.
authors.forename: Kung-Wen
authors.initials: KW
authors.lastname: Lu
authors.affiliation: School of Chinese Medicine for Post-Baccalaureate, I-Shou University, Kaohsiung, 84001, Taiwan.|Department of Chinese Medicine, E-Da Hospital, Kaohsiung, 82445, Taiwan.
authors.forename: Yi-Shih
authors.initials: YS
authors.lastname: Ma
authors.affiliation: Department of Nutrition and Health Science, Chang Jung Christian University, Tainan, 711, Taiwan.
authors.forename: Chih-Chung
authors.initials: CC
authors.lastname: Wu
authors.affiliation: Department of Clinical Pathology, Cheng Hsin General Hospital, Taipei, 112, Taiwan.
authors.forename: Hsu-Feng
authors.initials: HF
authors.lastname: Lu
authors.affiliation: Department of Medicinal Botany and Health Applications, Da-Yeh University, Changhua, 51591, Taiwan.
authors.forename: Jaw-Chyun
authors.initials: JC
authors.lastname: Chen
authors.affiliation: Graduate Institute of Chinese Medicine, China Medical University, Taichung, 404, Taiwan.
authors.forename: Jaung-Geng
authors.initials: JG
authors.lastname: Lin
authors.affiliation: School of Pharmacy, China Medical University, Taichung, 404, Taiwan. jgchung@mail.cmu.edu.tw.
authors.forename: Ping-Ping
authors.initials: PP
authors.lastname: Wu
authors.affiliation: Department of Biological Science and Technology, China Medical University, Taichung, 404, Taiwan. ppwu@mail.cmu.edu.tw.|Department of Biotechnology, Asia University, Taichung, 413, Taiwan, Republic of China. ppwu@mail.cmu.edu.tw.
authors.forename: Jing-Gung
authors.initials: JG
authors.lastname: Chung
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000378:metabolism; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D000081005:Cyclohexane Monoterpenes; D007938:Leukemia / Q000188:drug therapy / Q000473:pathology; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D039821:Monoterpenes / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000081005:Cyclohexane Monoterpenes; D039821:Monoterpenes; D017382:Reactive Oxygen Species; C005403:alpha phellandrene; D020169:Caspases
keywords: WEHI-3 cells; apoptosis; cell cycle arrest; in vitro; α-phellandrene (α-PA)