Tristetraprolin: a novel mediator of the anticancer properties of resveratrol.
Resveratrol is a natural compound that exhibits anticancer properties. Previous studies have proved that it can inhibit the proliferation of breast cancer cell lines and upregulate some cytokines such as cyclooxygenase-2 (COX-2) and vascular endothelial growth factor (VEGF). The initiation and progression of cancer are associated with the abnormal expression of multiple cytokines. Tristetraprolin (TTP), an mRNA-binding protein, is one of the key proteins that participate in regulating cytokine expression. Two different proliferation assays on MCF-7 cells showed that the cell proliferation rate significantly reduced following treatment with resveratrol. Most importantly, we found that resveratrol promoted TTP expression at both the mRNA and protein level in a dose- and time-dependent manner. In addition, the expression of COX-2 and VEGF were significantly suppressed by resveratrol while that of inducible nitric oxide synthase (iNOS) was upregulated. Lastly, the effects of resveratrol on both MCF-7 proliferation and expression of COX-2, VEGF, and iNOS were significantly inhibited by TTP knockdown, indicating that TTP mediates the anticancer properties of resveratrol. In summary, we conclude that resveratrol inhibits the proliferation of MCF-7 cells by TTP upregulation, which is associated with downregulation of COX-2 and VEGF and upregulation of iNOS.
Department of General Surgery, The First Affiliated Hospital, University of South China, HengYang, Hunan.
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Li
Department of General Surgery, The First Affiliated Hospital, University of South China, HengYang, Hunan.
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Tang
Department of General Surgery, The First Affiliated Hospital, University of South China, HengYang, Hunan.
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D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000096:biosynthesis / Q000235:genetics*; D052246:Cyclooxygenase 2 Inhibitors / Q000008:administration & dosage; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D055786:Gene Knockout Techniques; D006801:Humans; D061986:MCF-7 Cells; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis* / Q000235:genetics; D016601:RNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics; D000077185:Resveratrol; D013267:Stilbenes / Q000008:administration & dosage; D051816:Tristetraprolin / Q000037:antagonists & inhibitors / Q000235:genetics*; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis / Q000235:genetics*
D052246:Cyclooxygenase 2 Inhibitors; D016601:RNA-Binding Proteins; D013267:Stilbenes; D051816:Tristetraprolin; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C496319:NOS2 protein, human; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D000077185:Resveratrol