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. Berber...

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Bibliographic Details
Published in:Anticancer research 2007-09, Vol.27 (5A), p.3379-3386
Main Authors: Lin, Jing-Pin, Yang, Jai-Sing, Chang, Nai-Wen, Chiu, Tsan-Hung, Su, Chin-Cheng, Lu, Kung-Wen, Ho, Yung-Tsuan, Yeh, Chin-Chung, Mei-Dueyang, Lin, Hui-Ju, Chung, Jing-Gung
Format: Article
Language:English
Subjects:
Apoptosis - drug effects
Apoptosis - physiology
Berberine - pharmacology
Blotting, Western
Calcium - metabolism
Caspase 3 - metabolism
Cell Line, Tumor
Enzyme Activation
Female
Humans
Membrane Potential, Mitochondrial - drug effects
Membrane Potential, Mitochondrial - physiology
Reactive Oxygen Species - metabolism
Transcription Factor CHOP - biosynthesis
Uterine Cervical Neoplasms - drug therapy
Uterine Cervical Neoplasms - metabolism
Uterine Cervical Neoplasms - pathology
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Summary: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 Ca 2+ , disruption of the mitochondrial membrane potential, and promotion of caspase-3 activity. In CaSki cells pretreated with the pan-caspase inhibitor z-VAD-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 Ca 2+ release from the ER. When the Ca Ski cells were pretreated with catalase, GADD153 production was abrogated and apoptosis was significantly reduced.
ISSN:0250-7005
1791-7530