Journal
CANCER LETTERS
Volume 295, Issue 2, Pages 252-259Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2010.03.008
Keywords
Gallbladder carcinoma; Cirsimaritin; Apoptosis; Reactive oxygen species; Endoplasmic reticulum stress
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Funding
- National Natural Science Foundation of China [30640060, 30872502, 30972918]
- Natural Science Foundation of Zhejiang Province for Outstanding Young Researcher Groups [R2080452]
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In this study, the anticancer effect of cirsimaritin, a natural flavonoid, against human gallbladder carcinoma cell line GBC-SD and the underlying mechanisms were investigated. Cirsimaritin inhibited the growth of tumor cells and induced mitochondrial apoptosis in GBC-SD cells. In addition, cirsimaritin triggered endoplasmic reticulum (ER) stress and down-regulated the phosphorylation of Akt, while knock-down of CHOP dramatically abrogated the inactivation of Akt and reversed the pro-apoptotic effect of cirsimaritin. Furthermore, cirsimaritin provoked the generation of reactive oxygen species in GBC-SD cells, while the antioxidant N-acetyl cysteine almost completely blocked the activation of ER stress and apoptosis, suggesting cirsimaritin-induced reactive oxygen species is an early event that triggers ER stress mitochondrial apoptotic pathways in GBC-SD cells. (C) 2010 Elsevier Ireland Ltd. All rights reserved.
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