Journal Article

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

Joo Eun Jung, Hong Sook Kim, Chang Seok Lee, Dae-Hun Park, Yong-Nyun Kim, Min-Jae Lee, Jung Weon Lee, Jong-Wan Park, Myung-Suk Kim, Sang Kyu Ye and Myung-Hee Chung

in Carcinogenesis

Volume 28, issue 8, pages 1780-1787
Published in print August 2007 | ISSN: 0143-3334
Published online June 2007 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgm130
Caffeic acid and its synthetic derivative CADPE suppress tumor angiogenesis by blocking STAT3-mediated VEGF expression in human renal carcinoma cells

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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-1α (hypoxia inducible factor-1α) 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-1α activity. Consequently, sequential blockade of STAT3 and HIF-1α 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-1α 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-1α and VEGF.

Journal Article.  6022 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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