GADD153 mediates berberine-induced apoptosis in human cervical cancer Ca ski cells.
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.
Lin
Jing-Pin
JP
School of Chinese Medicine, Department of Pharmacology, China Medical University, Taichung City, 404, Taiwan, ROC.
Yang
Jai-Sing
JS
Chang
Nai-Wen
NW
Chiu
Tsan-Hung
TH
Su
Chin-Cheng
CC
Lu
Kung-Wen
KW
Ho
Yung-Tsuan
YT
Yeh
Chin-Chung
CC
Mei-Dueyang
Lin
Hui-Ju
HJ
Chung
Jing-Gung
JG
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
C497249:DDIT3 protein, human; D017382:Reactive Oxygen Species; D001599:Berberine; D051742:Transcription Factor CHOP; D053148:Caspase 3; D002118:Calcium