Reactive oxygen species-mediated endoplasmic reticulum stress and mitochondrial dysfunction contribute to polydatin-induced apoptosis in human nasopharyngeal carcinoma CNE cells

Abstract

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.

Xenobiotic Perturbation of ER Stress and the Unfolded Protein Response

“…Reduced ER stress/UPR activation with concomitant reduction of apoptosis in response to a variety of pro-ER stress stimuli Choi et al 2010a;Liu et al 2011;Sanson et al 2009;Shimazaki et al 2010 Dantrolene Ryanodine receptor antagonist…”

Polydatin improves glucose and lipid metabolism in experimental diabetes through activating the Akt signaling pathway

“…Moreover, the average polydatin concentration in P. cuspidatum is seven times that of resveratrol (Ravagnan et al, 2012). Previous studies have shown that polydatin had many effects on inflammation and oxidation by regulating reactive oxygen species (ROS) generation and mitochondrial function (Liu et al, 2011;Ji et al, 2012). In the past few years, the lipid regulation of polydatin has gained considerable attentions Xing et al, 2009), and a previous study has demonstrated that polydatin has a hypoglycemic effect on experimental diabetic rats (Peng et al, 2012).…”

Polydatin modulates Ca2+ handling, excitation–contraction coupling and β-adrenergic signaling in rat ventricular myocytes

“…PD has also been found to be one of the major stilbenoid compounds in red wine [10]. Similar to resveratrol, PD has multiple biological activities, including antioxidant, anti-inflammation, anti-platelete coagulation and anti-hyperlipidemia [9,[11][12][13]. A number of studies have shown that PD applied in vivo enhanced cardiac function and improved microcirculation in hemorrhagic shock and severe burn injury without interfering with normal hemodynamics [9,14].…”