PMID- 28487966 OWN - NLM STAT- MEDLINE DCOM- 20180226 LR - 20180226 IS - 1791-244X (Electronic) IS - 1107-3756 (Linking) VI - 39 IP - 6 DP - 2017 Jun TI - Oligomeric proanthocyanidins protects A549 cells against H2O2-induced oxidative stress via the Nrf2-ARE pathway. PG - 1548-1554 LID - 10.3892/ijmm.2017.2971 [doi] AB - Oxidative signaling and oxidative stress contribute to aging, cancer and diseases resulting from lung fibrosis. In this study, we explored the anti-oxidative potential of oligomeric proanthocyanidins (OPCs), natural flavonoid compounds. We examined the protective effects of OPCs against hydrogen peroxide (H2O2)-induced oxidative stress in non-small cell lung cancer cells (A549). We demonstrated that OPC markedly attenuated H2O2-induced A549 cell viability, as shown by by 3-[4,5-dimethylthiazol-2-yl)]-2,5-diphenyl-tetrazolium bromide (MTT) assay. At the same time, OPC inhibited H2O2-induced oxidative stress by significantly increasing the activities of superoxide dismutase, catalase and glutathione, and reducing the levels of reactive oxygen species (ROS) and malondialdehyde (MDA). Treatment of the A549 cells with OPC significantly promoted the nuclear translocation of NF-E2-related factor 2 (Nrf2) and significantly enhanced the expression of its target genes [heme oxygenase-1 (HO-1), NAD(P)H quinone dehydrogenase 1 (NQO1) and thioredoxin reductase 1 (TXNRD1)] with different fold change values at both the mRNA and protein level. The knockout of Nrf2 using CRISPR/Cas9 technology attenuated OPC-mediated ARE gene transcription, and almost abolished the OPC-mediated protective effects against H2O2-induced oxidative stress. On the whole, our study suggests that OPC plays an important role in controlling the antioxidant response of A549 cells via the Nrf2-ARE pathway. FAU - Sun, Chao AU - Sun C AD - Department of Cardiothoracic Surgery, Northern Jiangsu People's Hospital Affiliated to Yangzhou University, Yangzhou, Jiangsu 225001, P.R. China. FAU - Jin, Weiguo AU - Jin W AD - Department of Cardiothoracic Surgery, Northern Jiangsu People's Hospital Affiliated to Yangzhou University, Yangzhou, Jiangsu 225001, P.R. China. FAU - Shi, Hongcan AU - Shi H AD - Department of Cardiothoracic Surgery, Northern Jiangsu People's Hospital Affiliated to Yangzhou University, Yangzhou, Jiangsu 225001, P.R. China. LA - eng PT - Journal Article DEP - 20170427 PL - Greece TA - Int J Mol Med JT - International journal of molecular medicine JID - 9810955 RN - 0 (Antineoplastic Agents, Phytogenic) RN - 0 (Antioxidants) RN - 0 (NF-E2-Related Factor 2) RN - 0 (NFE2L2 protein, human) RN - 0 (Proanthocyanidins) RN - BBX060AN9V (Hydrogen Peroxide) SB - IM MH - A549 Cells MH - Antineoplastic Agents, Phytogenic/pharmacology MH - Antioxidant Response Elements/*drug effects MH - Antioxidants/*pharmacology MH - Gene Expression Regulation, Neoplastic/drug effects MH - Humans MH - Hydrogen Peroxide/metabolism MH - Lung Neoplasms/*drug therapy/genetics/metabolism MH - NF-E2-Related Factor 2/genetics/*metabolism MH - Oxidative Stress/drug effects MH - Proanthocyanidins/*pharmacology MH - Signal Transduction/*drug effects EDAT- 2017/05/11 06:00 MHDA- 2018/02/27 06:00 CRDT- 2017/05/11 06:00 PHST- 2016/02/06 00:00 [received] PHST- 2017/04/07 00:00 [accepted] PHST- 2017/05/11 06:00 [pubmed] PHST- 2018/02/27 06:00 [medline] PHST- 2017/05/11 06:00 [entrez] AID - 10.3892/ijmm.2017.2971 [doi] PST - ppublish SO - Int J Mol Med. 2017 Jun;39(6):1548-1554. doi: 10.3892/ijmm.2017.2971. Epub 2017 Apr 27.