RT Journal Article
SR Electronic
T1 GADD153 Mediates Berberine-induced Apoptosis in Human Cervical Cancer Ca Ski Cells
JF Anticancer Research
JO Anticancer Res
FD International Institute of Anticancer Research
SP 3379
OP 3386
VO 27
IS 5A
A1 LIN, JING-PIN
A1 YANG, JAI-SING
A1 CHANG, NAI-WEN
A1 CHIU, TSAN-HUNG
A1 SU, CHIN-CHENG
A1 LU, KUNG-WEN
A1 HO, YUNG-TSUAN
A1 YEH, CHIN-CHUNG
A1 YANG, MEI-DUE
A1 LIN, HUI-JU
A1 CHUNG, JING-GUNG
YR 2007
UL http://ar.iiarjournals.org/content/27/5A/3379.abstract
AB 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 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 Ca2+ release from the ER. When the Ca Ski cells were pretreated with catalase, GADD153 production was abrogated and apoptosis was significantly reduced. Copyright© 2007 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved