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.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Weis SM, Cheresh DA (2011) Tumor angiogenesis: molecular pathways and therapeutic targets. Nat Med 17(11):1359–1370
Vaupel P, Kallinowski F, Okunieff P (1989) Blood-flow, oxygen and nutrient supply, and metabolic microenvironment of human-tumors – a review. Cancer Res 49(23):6449–6465
Sagar SM, Yance D, Wong RK (2006) Natural health products that inhibit angiogenesis: a potential source for investigational new agents to treat cancer – part 2. Curr Oncol 13(3):99–107
Hill S, Williams KB, Denekamp J (1989) Vascular collapse after flavone acetic acid: a possible mechanism of its anti-tumour action. Eur J Cancer Clin Oncol 25(10):1419–1424
Middleton E Jr, Kandaswami C, Theoharides TC (2000) The effects of plant flavonoids on mammalian cells: implications for inflammation, heart disease, and cancer. Pharmacol Rev 52(4):673–751
Su JL, Yang PC, Shih JY et al (2006) The VEGF-C/Flt-4 axis promotes invasion and metastasis of cancer cells. Cancer Cell 9(3):209–223
Man SL, Gao WY, Wei CL et al (2012) Anticancer drugs from traditional toxic Chinese medicines. Phytother Res 26(10):1449–1465
Zhang M, Swarts SG, Yin LJ et al (2011) Antioxidant properties of quercetin. Oxygen Transp Tissue 701(Xxxii):283–289
Kuo SM (1997) Dietary flavonoid and cancer prevention: evidence and potential mechanism. Crit Rev Oncog 8(1):47–69
Kanadaswami C, Lee LT, Lee PPH et al (2005) The antitumor activities of flavonoids. In Vivo 19(5):895–909
Sanges D, Marigo V (2006) Cross-talk between two apoptotic pathways activated by endoplasmic reticulum stress: differential contribution of caspase-12 and AIF. Apoptosis 11(9):1629–1641
Acknowledgments
This project is supported by UF Health Cancer Center startup funds (University of Florida). We thank Kate Casey-Sawicki for editing this manuscript.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2014 Springer Science+Business Media, LLC
About this paper
Cite this paper
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
Download citation
DOI: https://doi.org/10.1007/978-1-4939-0620-8_20
Published:
Publisher Name: Springer, New York, NY
Print ISBN: 978-1-4939-0583-6
Online ISBN: 978-1-4939-0620-8
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)