Abstract Title:

Resveratrol inhibits pancreatic cancer cell proliferation through transcriptional induction of macrophage inhibitory cytokine-1.

Abstract Source:

J Surg Res. 2007 Apr;138(2):163-9. Epub 2007 Jan 25. PMID: 17257620

Abstract Author(s):

Laleh Golkar, Xian-Zhong Ding, Michael B Ujiki, Mohammad R Salabat, David L Kelly, Denise Scholtens, Angela J Fought, David J Bentrem, Mark S Talamonti, Richard H Bell, Thomas E Adrian

Abstract:

INTRODUCTION: Resveratrol is a phenolic compound found in grape skins, mulberries, and certain nuts that has been shown to have antitumorigenic and anti-inflammatory properties. Macrophage inhibitory cytokine (MIC-1) is a member of the transforming growth factor beta (TGF-beta) superfamily that has been shown to have antitumorigenic activity and is up-regulated in resveratrol-treated cancer cells. Resveratrol inhibits proliferation of human pancreatic cancer cells; however, the exact mechanism of action is not known. In this study, we investigated the role of MIC-1 in resveratrol-induced growth inhibition of human pancreatic cancer cell lines. METHODS AND RESULTS: Proliferation assays conducted with resveratrol-treated human pancreatic cancer cell lines (CD18 and S2-013) at 24, 48, and 72 h revealed inhibition of cell proliferation compared to controls. Using oligonucleotide microarray analysis, we identified marked up-regulation of MIC-1 gene expression in resveratrol-treated human pancreatic cancer S2-013 cells. Real-time RT-PCR performed in CD18 and S2-013 cells treated with resveratrol (0-100 mum) for 24 h confirmed concentration and time-dependent up-regulation of expression of one particular gene, MIC-1. Both cell lines pretreated with actinomycin D (a transcriptional inhibitor) and then resveratrol had reduced up-regulation of MIC-1 gene expression compared to those treated with resveratrol alone. Finally, resveratrol-induced growth inhibition was abolished in CD18 cells transfected with MIC-1 short interfering RNA. CONCLUSIONS: Resveratrol up-regulates MIC-1 gene expression in part at the transcriptional level in pancreatic cancer cells. Furthermore, MIC-1 appears to play a key role in resveratrol-induced growth inhibition in these cells.

 

Study Type : In Vitro Study

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