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Reactive oxygen species‐mediated endoplasmic reticulum stress and mitochondrial dysfunction contribute to polydatin‐induced apoptosis in human nasopharyngeal carcinoma CNE cells
Author(s) -
Liu Huanhai,
Zhao Shuwei,
Zhang Yinfang,
Wu Jian,
Peng Hu,
Fan Jingping,
Liao Jianchun
Publication year - 2011
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.23303
Subject(s) - endoplasmic reticulum , reactive oxygen species , apoptosis , unfolded protein response , oxidative stress , chemistry , microbiology and biotechnology , protein kinase b , mitochondrion , cancer research , biochemistry , biology
Previous studies revealed that polydatin, a natural small compound, possessed protective effect against ischemia/reperfusion injury and inflammation. However, the action and molecular mechanism of its potent anti‐cancer activity remain poorly understood. In the present study, polydatin significantly killed several human tumor cell lines in a dose‐ and time‐dependent manner. The compound also dose‐dependently caused mitochondrial apoptosis in human nasopharyngeal carcinoma CNE cells. In addition, polydatin triggered endoplasmic reticulum (ER) stress and down‐regulated the phosphorylation of Akt in CNE cells, while knock‐down of CCAAT/enhancer‐binding protein homologous protein (CHOP) dramatically abrogated the inactivation of Akt and reversed the pro‐apoptotic effect of polydatin. Furthermore, polydatin provoked the generation of reactive oxygen species in CNE cells, while the antioxidant N‐acetyl cysteine almost completely blocked the activation of ER stress and apoptosis, suggesting polydatin‐induced reactive oxygen species is an early event that triggers ER stress mitochondrial apoptotic pathways in CNE cells. Taken together, these findings strongly suggest that polydatin might be a promising anti‐tumor drug and our data provide the molecular theoretical basis for clinical application of polydatin. J. Cell. Biochem. 112: 3695–3703, 2011. © 2011 Wiley Periodicals, Inc.