Reactive oxygen species-mediated endoplasmic reticulum stress and mitochondrial dysfunction contribute to cirsimaritin-induced apoptosis in human gallbladder carcinoma GBC-SD cells.
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.
Quan
Zhiwei
Z
Department of General Surgery, Xinhua Hospital, Shanghai Jiao Tong University, China.
Gu
Jun
J
Dong
Ping
P
Lu
Jianhua
J
Wu
Xiangsong
X
Wu
Wenguang
W
Fei
Xiaozhou
X
Li
Songgang
S
Wang
Yong
Y
Wang
Jianwei
J
Liu
Yingbin
Y
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D045304:Cytochromes c / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000187:drug effects* / Q000378:metabolism; D047309:Flavones / Q000494:pharmacology*; D005706:Gallbladder Neoplasms / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000502:physiology*; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology; D017382:Reactive Oxygen Species / Q000378:metabolism*; D051742:Transcription Factor CHOP / Q000502:physiology
D000972:Antineoplastic Agents, Phytogenic; C497249:DDIT3 protein, human; D047309:Flavones; D017382:Reactive Oxygen Species; D051742:Transcription Factor CHOP; C007072:cirsimaritin; D045304:Cytochromes c; D051057:Proto-Oncogene Proteins c-akt; D020169:Caspases