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Molecules 2016, 21(5), 601;

Anticancer Activity of γ-Bisabolene in Human Neuroblastoma Cells via Induction of p53-Mediated Mitochondrial Apoptosis

Department of Medical Laboratory Science and Biotechnology, China Medical University, No. 91, Hsueh-Shih Road, Taichung 404, Taiwan
Department of Otolaryngology, China Medical University Hospital, Taichung 404, Taiwan
Division of Gastroenterology, Kuang Tien General Hospital, Taichung 433, Taiwan
Department of Medical Genetics and Medical Research, China Medical University Hospital, Taichung 404, Taiwan
Department of Biotechnology, College of Health Science, Asia University, Wufeng, Taichung 413, Taiwan
These authors contributed equally to this work.
Authors to whom correspondence should be addressed.
Academic Editor: Derek J. McPhee
Received: 23 March 2016 / Revised: 2 May 2016 / Accepted: 3 May 2016 / Published: 7 May 2016
(This article belongs to the Section Medicinal Chemistry)
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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. View Full-Text
Keywords: γ-bisabolene; neuroblastoma; anticancer; apoptosis; p53; CK2α γ-bisabolene; neuroblastoma; anticancer; apoptosis; p53; CK2α

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Jou, Y.-J.; Hua, C.-H.; Lin, C.-S.; Wang, C.-Y.; Wan, L.; Lin, Y.-J.; Huang, S.-H.; Lin, C.-W. Anticancer Activity of γ-Bisabolene in Human Neuroblastoma Cells via Induction of p53-Mediated Mitochondrial Apoptosis. Molecules 2016, 21, 601.

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