title: α-Phellandrene alters expression of genes associated with DNA damage, cell cycle, and apoptosis in murine leukemia WEHI-3 cells.
abstract: α-phellandrene (α-PA) is a cyclic monoterpene, present in natural plants such as Schinus molle L. α-PA promotes immune responses in mice in vivo. However, there is no available information on whether α-PA affects gene expression in leukemia cells. The present study determined effects of α-PA on expression levels of genes associated with DNA damage, cell cycle and apoptotic cell death in mouse leukemia WEHI-3 cells. WEHI-3 cells were treated with 10 μM α-PA for 24 h, cells were harvested and total RNA was extracted, and gene expression was analyzed by cDNA microarray. Results indicated that α-PA up-regulated 10 genes 4-fold, 13 by over 3-fold and 175 by over 2-fold; 21 genes were down-regulated by over 4-fold, 26 genes by over 3-fold and expression of 204 genes was altered by at leas 2-fold compared with the untreated control cells. DNA damage-associated genes such as DNA damage-inducer transcript 4 and DNA fragmentation factor were up-regulated by 4-fold and over 2-fold, respectively; cell-cycle check point genes such as cyclin G2 and cyclin-dependent kinases inhibitor 2D and IA (p21) were up-regulated by over 3-fold and over 2-fold, respectively; apoptosis-associated genes such as BCL2/adenovirus EIB interacting protein 3, XIAP-associated factor 1, BCL2 modifying factor, caspase-8 and FADD-like apoptosis regulator were over 2-fold up-regulated. Furthermore, DNA damage-associated gene TATA box binding protein was over 4-fold down-regulated, and D19Ertd652c (DNA segment) over 2-fold down-regulated; cell cycle-associated gene cyclin E2 was over 2-fold down-regulated; apoptosis associated gene growth arrest-specific 5 was over 9-fold down-regulated, Gm5426 (ATP synthase) was over 3-fold down-regulated, and death box polypeptide 33 was over 2-fold down-regulated. Based on these observations, α-PA altered gene expression in WEHI-3 cells in vitro.
authors: Graduate Institute of Chinese Medicine, China Medical University, Taichung, Taiwan, R.O.C. Division of Cardiology, China Medical University Hospital, Taichung, Taiwan, R.O.C.
authors: Jen-Jyh
authors: JJ
authors: Lin
authors: School of Pharmacy, China Medical University, Taichung, Taiwan, R.O.C.
authors: Chien-Chih
authors: CC
authors: Yu
authors: Graduate Institute of Chinese Medicine, China Medical University, Taichung, Taiwan, R.O.C.
authors: Kung-Wen
authors: KW
authors: Lu
authors: School of Pharmacy, China Medical University, Taichung, Taiwan, R.O.C.
authors: Shu-Jen
authors: SJ
authors: Chang
authors: Department of Dentistry, China Medical University, Taichung, Taiwan, R.O.C.
authors: Fu-Shun
authors: FS
authors: Yu
authors: Graduate Institute of Chinese Medicine, China Medical University, Taichung, Taiwan, R.O.C.
authors: Ching-Lung
authors: CL
authors: Liao
authors: Graduate Institute of Chinese Medicine, China Medical University, Taichung, Taiwan, R.O.C. jgchung@mail.cmu.edu.tw jglin@mail.cmu.edu.tw.
authors: Jaung-Geng
authors: JG
authors: Lin
authors: Department of Biological Science and Technology, China Medical University, Taichung, Taiwan, R.O.C. Department of Biotechnology, Asia University, Taichung, Taiwan, R.O.C. jgchung@mail.cmu.edu.tw jglin@mail.cmu.edu.tw.
authors: Jing-Gung
authors: JG
authors: Chung
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects*; D045744:Cell Line, Tumor; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics; D016213:Cyclins / Q000235:genetics; D000081005:Cyclohexane Monoterpenes; D004249:DNA Damage; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects*; D051379:Mice; D039821:Monoterpenes / Q000494:pharmacology*; D020411:Oligonucleotide Array Sequence Analysis
chemical_list: C493956:CDKN1A protein, human; C503689:Ccne2 protein, mouse; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D000081005:Cyclohexane Monoterpenes; D039821:Monoterpenes; C005403:alpha phellandrene
keywords: DNA damage; WEHI-3 leukemia cells; apoptosis; cDNA microarray; cell cycle; α-Phellandrene