title: GADD153 mediates berberine-induced apoptosis in human cervical cancer Ca ski cells.
abstract: Berberine, an isoquinoline alkaloid, has been shown to possess anticancer properties in some cancer cell lines. Here, we report that in vitro treatment of cervical cancer Ca Ski cells with berberine decreased the percentage of viable Ca Ski cells in a dose-dependent and time-dependent manner. Berberine enhanced the apoptosis of Ca Ski cells with the induction of a higher ratio of p53 and Bax/Bcl-2 proteins, increased levels of reactive oxygen species (ROS) and Ca2+, disruption of the mitochondrial membrane potential, and promotion of caspase-3 activity. In CaSki cells pretreated with the pan-caspase inhibitor zVAD-fmk, the berberine-induced caspase-3 activity and apoptosis were significantly blocked as confirmed by flow cytometric analysis. Western blot also showed that berberine induced the expression of GADD153, a transcription factor involved in apoptosis. Thus berberine increased ROS levels leading to endoplasmic reticulum (ER) stress based on the increase of GADD153 and shown by Ca2+ release from the ER. When the Ca Ski cells were pretreated with catalase, GADD153 production was abrogated and apoptosis was significantly reduced.
authors.affiliation: School of Chinese Medicine, Department of Pharmacology, China Medical University, Taichung City, 404, Taiwan, ROC.
authors.forename: Jing-Pin
authors.initials: JP
authors.lastname: Lin
authors.forename: Jai-Sing
authors.initials: JS
authors.lastname: Yang
authors.forename: Nai-Wen
authors.initials: NW
authors.lastname: Chang
authors.forename: Tsan-Hung
authors.initials: TH
authors.lastname: Chiu
authors.forename: Chin-Cheng
authors.initials: CC
authors.lastname: Su
authors.forename: Kung-Wen
authors.initials: KW
authors.lastname: Lu
authors.forename: Yung-Tsuan
authors.initials: YT
authors.lastname: Ho
authors.forename: Chin-Chung
authors.initials: CC
authors.lastname: Yeh
authors.lastname: Mei-Dueyang
authors.forename: Hui-Ju
authors.initials: HJ
authors.lastname: Lin
authors.forename: Jing-Gung
authors.initials: JG
authors.lastname: Chung
mesh_terms: D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D001599:Berberine / Q000494:pharmacology*; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D004789:Enzyme Activation; D005260:Female; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects / Q000502:physiology; D017382:Reactive Oxygen Species / Q000378:metabolism; D051742:Transcription Factor CHOP / Q000096:biosynthesis*; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology
chemical_list: C497249:DDIT3 protein, human; D017382:Reactive Oxygen Species; D001599:Berberine; D051742:Transcription Factor CHOP; D053148:Caspase 3; D002118:Calcium