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  • Poster Presentation
  • Open Access

6-(1-oxobutyl)-5,8-dimethoxy-1,4-naphthoquinone exerts anti-angiogenic activity via inhibition of vascular endothelial cell growth factor and hypoxia-inducible factor 1 alpha in hypoxia-exposed MCF breast cancer cells

  • 1 and
  • 1
Breast Cancer Research20057 (Suppl 2) :P4.01

https://doi.org/10.1186/bcr1131

  • Published:

Keywords

  • Breast Cancer Cell
  • Fibroblast Growth Factor
  • Human Umbilical Vein Endothelial Cell
  • Human Breast Cancer Cell
  • Tube Formation

Background

Hypoxia induces the transcription of various genes involved in angiogenesis and anaerobic metabolism necessary for the growth of tumor cells. Hypoxia-inducible factor 1 alpha (HIF-1α) regulates genes involved in the response to hypoxia and promotes neo-angiogenesis in cancer. Thus, to develop an anticancer agent with anti-angiogenic activity in hypoxic cancer cells, 6-(1-oxobutyl)-5,8-dimetoxy-1,4-naphthoquinone (OXO) was synthesized.

Methods

The XTT (2,3-bis [2-methoxy-4-nitro-5-sulfophenyl]-2H-tetra-zolium-5-carboxanilide) assay for cytotoxicity, the ELISA, RT-PCR and western blotting analysis were employed in MCF-7 human breast cancer cells under hypoxic conditions.

Results

OXO showed cytotoxicity against MCF-7 cells, human breast M. OXO also reduced the levels cancer cells with an IC50 value of 10 μ of vascular endothelial cell growth factor (VEGF) and HIF-1α in MCF cells exposed to hypoxia. Similarly, OXO downregulated the expression of HIF-1 and VEGF by western blotting and RT-PCR. In addition, OXO inhibited the basic fibroblast growth factor (bFGF)-induced proliferation, inhibited tube formation of human umbilical vein endothelial cells (HUVECs) and also disrupted the neovascularization in bFGF-treated Matrigel in vivo.

Conclusion

Taken together, these results show that OXO may exert anti-tumor and anti-angiogenic activity against MCF-7 cells via regulation of HIF-1α and VEGF.
Figure 1
Figure 1

Cytotoxicity.

Figure 2
Figure 2

Effect of OXO on the proliferation of bFGF-treated HUVECs.

Figure 3
Figure 3

Effect of OXO on the tube formation of bFGF-treated HUVECs.

Figure 4
Figure 4

Effect of OXO on VEGF and HIF-1α in MCF-7 cells exposed to hypoxia.

Figure 5
Figure 5

Effect of OXO on the content of hemoglobin in bFGF-treated Matrigel.

Authors’ Affiliations

(1)
Department of Oncology, Graduate School of East-West Medical Science, Kyunghee University, Yongin, South Korea

References

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Copyright

© BioMed Central 2005

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