The novel targets for anti-angiogenesis of genistein on human cancer cells

Shu Jem Su, Trai Ming Yeh, Woei Jer Chuang, Chung Liang Ho, Kee Lung Chang, Hsiao Ling Cheng, Hsiao Sheng Liu, Hong Lin Cheng, Pei Yin Hsu, Nan Haw Chow

Research output: Contribution to journalArticle

99 Citations (Scopus)

Abstract

Genistein has been reported to be a natural chemopreventive in several types of human cancer. In our prior study, soy isoflavones were shown to induce cell cycle arrest and apoptosis of bladder cancer cells in the range of human urine excretion. This study was designed to identify the novel molecular basis underlying anti-angiogenic activities of soy isoflavones. An immortalized E6 and five human bladder cancer cell lines were studied by immunoassay, flow cytometry, functional activity, reverse transcription-polymerase chain reaction, immunoblotting, and transwell co-culture in vitro. The efficacy of soy isoflavones on angiogenesis inhibition in vivo was examined by nude mice xenograft and chick chorioallantoic membrane bioassay. Factors analyzed included angiogenic factors, matrix-degrading enzymes, and angiogenesis inhibitors. Genistein was the most potent inhibitor of angiogenesis in vitro and in vivo among the isoflavone compounds tested. It may also account for most of the reduced microvessel density of xenografts observed and the suppressed endothelial migration by soy isoflavones. Genistein exhibited a dose-dependent inhibition of expression/excretion of vascular endothelial growth factories, platelet-derived growth factor, tissue factor, urokinase plasminogen activator, and matrix metalloprotease-2 and 9, respectively. On the other hand, there was an up-regulation of angiogenesis inhibitors-plasminogen activator inhibitor-1, endostatin, angiostatin, and thrombospondin-1. In addition, a differential inhibitory effect between immortalized uroepithelial cells and most cancer cell lines was also observed. Altogether, we discovered that tissue factor, endostatin, and angiostatin are novel molecular targets of genistein. The current investigation provides further evidence in support of soy-based foods as natural dietary inhibitors of tumor angiogenesis.

Original languageEnglish
Pages (from-to)307-318
Number of pages12
JournalBiochemical Pharmacology
Volume69
Issue number2
DOIs
Publication statusPublished - 2005 Jan 15

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Pharmacology

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