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A New Flavonoid Regulates Angiogenesis and Reactive Oxygen Species Production

  • Mei Zhang
  • Chaomei Liu
  • Zhenhuan Zhang
  • Shanmin Yang
  • Bingrong Zhang
  • Liangjie Yin
  • Steven Swarts
  • Sadasivan Vidyasagar
  • Lurong Zhang
  • Paul Okunieff
Conference paper
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 812)

Abstract

The tumor vascular system, which is critical to the survival and growth of solid tumors, has been an attractive target for anticancer research. Building on studies that show that some flavonoids have anticancer vascular effects, we developed and analyzed the flavonoid derivative R24 [3, 6-bis (2-oxiranylmethoxy)-9H-xanthen-9-one]. A CAM assay revealed that R24 disrupted neovascular formation; fewer dendrites were detected and overall dendritic length was shorter in the R24-treated chicken embryos. The antiproliferative effect of R24 was measured by MTT assay in A549 (lung cancer), AsPC-1 (pancreatic cancer), HCT-116 (colorectal cancer), and PC-3 (prostate cancer) cell lines. R24 reduced proliferation with an IC50 of 3.44, 3.59, 1.22, and 11.83 μM, respectively. Cell-cycle analysis and Annexin-V/propidium iodide staining showed that R24 induced apoptosis. In addition, R24 regulated intracellular ROS production in a dose-dependent manner. CM-H2DCFDA staining indicated that intracellular ROS production increased with the R24 dose. In summary, we found that R24 exhibits potent antiangiogenic and antiproliferative effects, induces apoptosis, and promotes ROS production.

Keywords

Flavonoid Angiogenesis Reactive oxygen species Tumor vasculature Apoptosis 

Notes

Acknowledgments

This project is supported by UF Health Cancer Center startup funds (University of Florida). We thank Kate Casey-Sawicki for editing this manuscript.

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Copyright information

© Springer Science+Business Media, LLC 2014

Authors and Affiliations

  • Mei Zhang
    • 1
  • Chaomei Liu
    • 1
  • Zhenhuan Zhang
    • 1
  • Shanmin Yang
    • 1
  • Bingrong Zhang
    • 1
  • Liangjie Yin
    • 1
  • Steven Swarts
    • 1
  • Sadasivan Vidyasagar
    • 1
  • Lurong Zhang
    • 1
  • Paul Okunieff
    • 1
  1. 1.Department of Radiation OncologyUniversity of Florida, Cancer/Genetics Research ComplexGainesvilleUSA

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