Poster Presentation 26th Lorne Cancer Conference 2014

Inhibition of Tumour Angiogenesis as a means to reduce cancer growth by novel Benzoaxines (#102)

Sara Al-Rawi 1 , Terri Meehan-Andrews 1 , Chris Bradley 1
  1. La Trobe University, Kennington, VIC, Australia

Inhibition of tumour angiogenesis, as a means of reducing the growth of cancers, has become a promising target for adjuvant therapies. Angiogenesis begins with the proliferation of endothelial cells, followed by their migration and structural reorganisation into tubal structures, which align to form the new blood vessel. The DNA-PK and PI3K inhibitors LY249002 and its newer derivative NU7026 have been found to have anti angiogenic effects on endothelial cells by inhibiting proliferation and tube formation (1). In this study we utilise the primary endothelial cell line (HUVEC) and novel benzoaxine analogues of LY294002, to determine if they have similar anti angiogenic effect on endothelial cells with less toxic side effects. Seven benzoaxines have been developed with varying inhibitory potencies on DNA-PK. None of the compounds were found to be toxic at concentrations up to 5um. To determine their effect on the angiogenic process, we analysed proliferation, migration and tube formation of HUVECs at various concentrations. The effect on proliferation (SRB assay) identified 2 compounds (LTUSi112 and LTUT5) that had a significant inhibitory effect. These same compounds also showed significant inhibition on migration, determined using both the ‘scratch assay’ and the Boyden’s chamber. To determine the effect on tube formation, cells were cultured on growth ECM (Geltrex), after 18 hours in culture the number of complete tubes formed was counted as a measure of tube formation. The inhibitory effect of LTUSi122 and LTUT5 continued resulting in less tubes being formed. Our findings indicate that the benzoaxines, LTUSi122 and LTUT5, are potent inhibitors of several aspects of the angiogenic process, which used in combination with more targeted therapies could reduce tumour growth and increase the efficacy of these treatments.


Mannell, H., Hammitzsch, A., Mettler, R., Pohl, U., & Krotz, F. (2010). Suppression of DNA-PKcs enhances FGF-2 dependent human endothelial cell proliferation via negative regulation of Akt. Cell Signal, 22(1), 88-96.