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Caffeic acid and its synthetic derivative CADPE suppress tumor angiogenesis by blocking STAT3-mediated VEGF expression in human renal carcinoma cells

Cited 83 time in Web of Science Cited 92 time in Scopus
Authors
Jung, Joo Eun; Kim, Hong Sook; Lee, Chang Seok; Park, Dae-Hun; Kim, Yong-Nyun; Lee, Min-Jae; Lee, Jung Weon; Park, Jong-Wan; Kim, Myung-Suk; Ye, Sang Kyu; Chung, Myung-Hee
Issue Date
2007-06-15
Publisher
Oxford University Press
Citation
Carcinogenesis. 2007 Aug;28(8):1780-7. Epub 2007 Jun 8.
Keywords
Active Transport, Cell Nucleus/drug effectsAngiogenesis Inhibitors/*pharmacologyAnimalsAnoxia/metabolism/prevention & controlAntineoplastic Agents/*pharmacologyCOS CellsCaffeic Acids/*pharmacologyCarcinoma, Renal Cell/*drug therapy/*metabolismCell Line, TumorCercopithecus aethiopsHumansMaleMiceMice, Inbred BALB CMice, NudeNeovascularization, Pathologic/*drug therapySTAT3 Transcription Factor/*antagonists & inhibitors/physiologyVascular Endothelial Growth Factor A/*antagonists &inhibitors/biosynthesis/genetics
Abstract
Tumor angiogenesis is required for tumor development and is stimulated by angiogenic inducers like VEGF (vascular endothelial growth factor). Our previous study demonstrated that STAT3 (signal transducer and activator of transcription 3) up-regulates HIF-1alpha (hypoxia inducible factor-1alpha) protein stability and enhances HIF-1-mediated VEGF expression in hypoxic solid tumor cells, thus suggesting that the inhibition of STAT3 signaling may have clinical applications. In this study, we examined in vitro and in vivo, whether caffeic acid (CA) or its derivative CADPE [3-(3,4-dihydroxy-phenyl)-acrylic acid 2-(3,4-dihydroxy-phenyl)-ethyl ester] exert anticancer activity by targeting STAT3. It was found that CA or CADPE significantly inhibit STAT3 activity, and that this in turn down-regulates HIF-1alpha activity. Consequently, sequential blockade of STAT3 and HIF-1alpha resulted in the down-regulation of VEGF by inhibiting their recruitment to the VEGF promoter. In mice bearing a Caki-I carcinoma, both CA and CADPE retarded tumor growth and suppressed STAT3 phosphorylation, HIF-1alpha expression, vascularization and STAT3-inducible VEGF gene expression in tumors. Taken together, our results demonstrate that CA and CADPE are potential inhibitors of STAT3 and that they suppress tumor angiogenesis by inhibiting the activity of STAT3, the expression of HIF-1alpha and VEGF.
ISSN
0143-3334 (Print)
Language
English
URI
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17557905

http://hdl.handle.net/10371/29399
DOI
https://doi.org/10.1093/carcin/bgm130
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College of Medicine/School of Medicine (의과대학/대학원)Program in Cancer Biology (협동과정-종양생물학전공)Journal Papers (저널논문_협동과정-종양생물학전공)
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