Abstract |
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.
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Authors | Zhiwei Quan, Jun Gu, Ping Dong, Jianhua Lu, Xiangsong Wu, Wenguang Wu, Xiaozhou Fei, Songgang Li, Yong Wang, Jianwei Wang, Yingbin Liu |
Journal | Cancer letters
(Cancer Lett)
Vol. 295
Issue 2
Pg. 252-9
(Sep 28 2010)
ISSN: 1872-7980 [Electronic] Ireland |
PMID | 20359814
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | 2010 Elsevier Ireland Ltd. All rights reserved. |
Chemical References |
- Antineoplastic Agents, Phytogenic
- DDIT3 protein, human
- Flavones
- Reactive Oxygen Species
- Transcription Factor CHOP
- cirsimaritin
- Cytochromes c
- Proto-Oncogene Proteins c-akt
- Caspases
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Topics |
- Antineoplastic Agents, Phytogenic
(pharmacology)
- Apoptosis
(drug effects)
- Caspases
(metabolism)
- Cell Line, Tumor
- Cytochromes c
(metabolism)
- Endoplasmic Reticulum
(drug effects, metabolism)
- Flavones
(pharmacology)
- Gallbladder Neoplasms
(drug therapy, pathology)
- Humans
- Membrane Potential, Mitochondrial
(drug effects)
- Mitochondria
(physiology)
- Proto-Oncogene Proteins c-akt
(physiology)
- Reactive Oxygen Species
(metabolism)
- Transcription Factor CHOP
(physiology)
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