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Pterostilbene exerts anticancer activity on non-small-cell lung cancer via activating endoplasmic reticulum stress.

ABSTRACT: Pterostilbene (PT), the natural dimethylated analog of resveratrol (RSV), is a potent anticarcinogen for non-small-cell lung cancer (NSCLC), but its anti-NSCLC mechanisms remain unclear. In this study, we show that PT treatment time- and dose-dependently enhanced the endoplasmic reticulum stress (ERS) signaling (i.e., p-PERK, IRE1, ATF4, CHOP), thus decreasing the cell viability and inducing apoptosis in human PC9 and A549 NSCLC cell lines. Moreover, the decreased migratory and adhesive abilities, downregulation of intracellular glutathione (GSH) level, enhanced reactive oxygen species (ROS) generation, Caspase 3 activity and mitochondrial membrane depolarization were observed in NSCLC cells treated with PT. These effects were reversed by CHOP siRNA which inhibited the ERS signaling pathway, but were promoted by thapsigargin (a classical ERS inducer) in vitro. Besides, in vivo studies also verify that PT exerted anticancer activity by mobilizing ERS signaling and apoptosis-related proteins, and these effects were enhanced by thapsigargin. Therefore, ERS activation may represent a new mechanism of anti-NSCLC action by PT, and a novel therapeutic intervention for lung cancer.

SUBMITTER: Ma Z

PROVIDER: S-EPMC5556085 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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Pterostilbene exerts anticancer activity on non-small-cell lung cancer via activating endoplasmic reticulum stress.

Ma Zhiqiang Z Yang Yang Y Di Shouyin S Feng Xiao X Liu Dong D Jiang Shuai S Hu Wei W Qin Zhigang Z Li Yue Y Lv Jianjun J Fan Chongxi C Yan Xiaolong X Li Xiaofei X

Scientific reports 20170814 1

Pterostilbene (PT), the natural dimethylated analog of resveratrol (RSV), is a potent anticarcinogen for non-small-cell lung cancer (NSCLC), but its anti-NSCLC mechanisms remain unclear. In this study, we show that PT treatment time- and dose-dependently enhanced the endoplasmic reticulum stress (ERS) signaling (i.e., p-PERK, IRE1, ATF4, CHOP), thus decreasing the cell viability and inducing apoptosis in human PC9 and A549 NSCLC cell lines. Moreover, the decreased migratory and adhesive abilitie ...[more]

PMID: 28808300

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Project description:This investigation evaluated the potential of natural antioxidants, pterostilbene (PT) and its parent compound resveratrol (RSV), to alleviate hepatic damage, redox imbalance, mitochondrial dysfunction, and endoplasmic reticulum (ER) stress in early-weaned piglets. A total of 144 suckling piglets were randomly assigned to four treatments (six replicates per group, n = 6): 1) sow reared, 2) early weaned and fed a basal diet, 3) early weaned and fed the basal diet supplemented with 300 mg/kg PT, or with 4) 300 mg/kg RSV. Early weaning increased plasma alanine aminotransferase (P = 0.004) and aspartate aminotransferase (P = 0.009) activities and hepatic apoptotic rate (P = 0.001) in piglets compared with the sow-reared piglets. Early weaning decreased hepatic adenosine triphosphate (ATP; P = 0.006) content and mitochondrial complexes III (P = 0.019) and IV activities (P = 0.038), but it increased superoxide anion accumulation (P = 0.026) and the expression levels of ER stress markers, such as glucose-regulated protein 78 (P < 0.001), CCAAT/enhancer-binding protein-homologous protein (P = 0.001), and activating transcription factor (ATF) 4 (P = 0.006). PT was superior to RSV at mitigating liver injury and oxidative stress after early weaning, as indicated by decreases in the number of apoptotic cells (P = 0.036) and the levels of superoxide anion (P = 0.002) and 8-hydroxy-2 deoxyguanosine (P < 0.001). PT increased mitochondrial deoxyribonucleic acid content (P = 0.031) and the activities of citrate synthase (P = 0.005), complexes I (P = 0.004) and III (P = 0.011), and ATP synthase (P = 0.041), which may contribute to the mitigation of hepatic ATP deficit (P = 0.017) in the PT-treated weaned piglets. PT also prevented increases in the ER stress marker and ATF 6 expression levels and in the phosphorylation of inositol-requiring enzyme 1 alpha caused by early weaning (P < 0.05). PT increased sirtuin 1 activity (P = 0.031) in the liver of early-weaned piglets than those in the early-weaned piglets fed a basal diet. In conclusion, PT supplementation alleviates liver injury in weanling piglets probably by inhibiting mitochondrial dysfunction and ER stress.

Dataset Information

Pterostilbene exerts anticancer activity on non-small-cell lung cancer via activating endoplasmic reticulum stress.

Publications

Pterostilbene exerts anticancer activity on non-small-cell lung cancer via activating endoplasmic reticulum stress.

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