Resveratrol modulates mRNA transcripts of genes related to redox metabolism and cell proliferation in non-small-cell lung carcinoma cells.
Resveratrol is a polyphenolic chemopreventive agent that has been shown to influence cellular redox reactions. As a systematic approach to elucidating the complex effects of resveratrol on eukaryotic cells, we studied its dose-dependent effects on the transcript levels of genes and activities of enzymes related to redox metabolism, cell cycle regulation, and apoptotic cascades in the cancer cell line A549. Glutathione peroxidase (GPx)1 mRNA levels, as well as GPx and thioredoxin reductase (TrxR) activities, were significantly increased after resveratrol treatment, whereas total glutathione concentrations decreased. Increased transcript levels were also detected for selenophosphate synthetase 2 and superoxide dismutase 2. However, mRNA levels of thioredoxin, TrxR, glutathione reductase, glutathione S-transferase, superoxide dismutase 1, and catalase were not altered. Among the 12 genes studied that are related to the cell cycle, differentiation and apoptosis, mRNA levels of six genes, including P53, FAS, and BCL2, were upregulated, while the mRNA level of survivin was reduced. The results suggest that GPx and other selenoproteins are important targets of resveratrol. Furthermore, genes supporting cell survival and differentiation, as well as genes involved in proliferation inhibition and apoptosis, are induced by resveratrol, resulting in a delicate balance that is likely to contribute to the chemopreventive effects of resveratrol.
Hu
Ying
Y
Nutritional Biochemistry, Interdisciplinary Research Center, Justus-Liebig-University Giessen, and Faculty of Medicine, Institute of Indoor and Environmental Toxicology, University Hospital of Giessen and Marburg, Germany.
Rahlfs
Stefan
S
Mersch-Sundermann
Volker
V
Becker
Katja
K
D017209:Apoptosis / Q000187:drug effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000378:metabolism*; D002452:Cell Count; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005978:Glutathione / Q000187:drug effects; D005979:Glutathione Peroxidase / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D010084:Oxidation-Reduction; D010770:Phosphotransferases / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism*; D000077185:Resveratrol; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D013267:Stilbenes / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014158:Transcription, Genetic / Q000187:drug effects* / Q000235:genetics; D014407:Tumor Cells, Cultured; D000094765:Glutathione Peroxidase GPX1
D012333:RNA, Messenger; D013267:Stilbenes; D005979:Glutathione Peroxidase; D010770:Phosphotransferases; C062762:selenophosphate synthetase; D005978:Glutathione; D000077185:Resveratrol; D000094765:Glutathione Peroxidase GPX1; C000722067:GPX1 protein, human