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.
Mei Zhang and Chaomei Liu contributed equally to this work.
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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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Zhang, M. et al. (2014). A New Flavonoid Regulates Angiogenesis and Reactive Oxygen Species Production. In: Swartz, H.M., Harrison, D.K., Bruley, D.F. (eds) Oxygen Transport to Tissue XXXVI. Advances in Experimental Medicine and Biology, vol 812. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-0620-8_20
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DOI: https://doi.org/10.1007/978-1-4939-0620-8_20
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