title: Anticancer Activity of γ-Bisabolene in Human Neuroblastoma Cells via Induction of p53-Mediated Mitochondrial Apoptosis.
abstract: γ-Bisabolene has demonstrated antiproliferative activities against several human cancer cell lines. This study first discloses the antiproliferative and apoptosis induction activities of γ-bisabolene to human neuroblastoma TE671 cells. A CC50 value of γ-bisabolene was 8.2 μM to TE671 cells. Cell cycle analysis with PI staining showed γ-bisabolene elevating the sub-G1 fractions in a time-dependent manner. In addition, annexin V-FITC/PI staining showed γ-bisabolene significantly triggering early (annexin-V positive/PI negative) and late (annexin-V positive/PI positive) apoptosis in dose-dependent manners. γ-Bisabolene induced caspase 3/8/9 activation, intracellular ROS increase, and mitochondrial membrane potential decrease in apoptosis of human neuro-blastoma cells. Moreover, γ-bisabolene increased p53 phosphorylation and up-regulated p53-mediated apoptotic genes Bim and PUMA, as well as decreased the mRNA and protein levels of CK2α. Notably, the results indicated the involvement of CK2α-p53 pathways in mitochondria-mediated apoptosis of human neuroblastoma cells treated with γ-bisabolene. This study elucidated the apoptosis induction pathways of γ-bisabolene-treated neuroblastoma cells, in which could be useful for developing anti-neuroblastoma drugs.
authors.affiliation: Department of Medical Laboratory Science and Biotechnology, China Medical University, No. 91, Hsueh-Shih Road, Taichung 404, Taiwan. alvajou@gmail.com.
authors.forename: Yu-Jen
authors.initials: YJ
authors.lastname: Jou
authors.affiliation: Department of Otolaryngology, China Medical University Hospital, Taichung 404, Taiwan. flowererix@yahoo.com.tw.
authors.forename: Chun-Hung
authors.initials: CH
authors.lastname: Hua
authors.affiliation: Division of Gastroenterology, Kuang Tien General Hospital, Taichung 433, Taiwan. b8401126@yahoo.com.tw.
authors.forename: Chen-Sheng
authors.initials: CS
authors.lastname: Lin
authors.affiliation: Department of Medical Laboratory Science and Biotechnology, China Medical University, No. 91, Hsueh-Shih Road, Taichung 404, Taiwan. spirit1126@hotmail.com.
authors.forename: Ching-Ying
authors.initials: CY
authors.lastname: Wang
authors.affiliation: Department of Medical Genetics and Medical Research, China Medical University Hospital, Taichung 404, Taiwan. lei.joseph@gmail.com.
authors.forename: Lei
authors.initials: L
authors.lastname: Wan
authors.affiliation: Department of Medical Genetics and Medical Research, China Medical University Hospital, Taichung 404, Taiwan. yjlin.kath@gmail.com.
authors.forename: Ying-Ju
authors.initials: YJ
authors.lastname: Lin
authors.affiliation: Department of Biotechnology, College of Health Science, Asia University, Wufeng, Taichung 413, Taiwan. shhuang@asia.edu.tw.
authors.forename: Su-Hua
authors.initials: SH
authors.lastname: Huang
authors.affiliation: Department of Medical Laboratory Science and Biotechnology, China Medical University, No. 91, Hsueh-Shih Road, Taichung 404, Taiwan. cwlin@mail.cmu.edu.tw.|Department of Biotechnology, College of Health Science, Asia University, Wufeng, Taichung 413, Taiwan. cwlin@mail.cmu.edu.tw.
authors.forename: Cheng-Wen
authors.initials: CW
authors.lastname: Lin
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D047390:Casein Kinase II / Q000235:genetics / Q000378:metabolism; D020169:Caspases / Q000378:metabolism; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects*; D009447:Neuroblastoma / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism*; D012717:Sesquiterpenes / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D012717:Sesquiterpenes; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C511058:gamma-bisabolene; D047390:Casein Kinase II; D020169:Caspases
keywords: CK2α; anticancer; apoptosis; neuroblastoma; p53; γ-bisabolene