Immune-modulating and anti-vascular activities of two xanthenone acetic acid analogues: A comparative study to DMXAA

  • Authors:
    • Mariagnese Barbera
    • Mikko I. Kettunen
    • Anna Caputo
    • De-En Hu
    • Silvia Gobbi
    • Kevin M. Brindle
    • Maria Carrara
  • View Affiliations

  • Published online on: January 1, 2009     https://doi.org/10.3892/ijo_00000149
  • Pages: 273-279
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Abstract

In order to proliferate, solid tumours require the development and continuous expansion of an organised host-derived vascular network. The anti-vascular agent 5,6-dimethylxanthenone-4-acetic acid (DMXAA) emerged as derivative of the flavone-8-acetic acid (FAA) and xanthenone-4-acetic acid (XAA). Its anti-vascular activity is not based on direct cytotoxic effects, but is characterized by an immune-mediated component, through the activation of NF-κB pathway, and a direct anti-vascular action, involving the induction of endothelial cell apoptosis and changes in tumour vessel permeability. Despite promising pre-clinical results, DMXAA showed moderate anti-tumour activity in clinical trials. In this study, we compared to DMXAA the in vitro immune-modulating and the anti-vascular properties of two XAA analogues, AP/1649 and AP/1897. Their immune-stimulating activities were evaluated on a human monocyte cell line and their anti-vascular activities were studied by measuring the induction of HUVECs apoptosis and using DCE-MRI to determine tumour perfusion following drug treatment. Although the two molecules exerted an immune stimulation comparable to that produced by DMXAA, they showed reduced (AP/1649) or minimal (AP/1897) anti-vascular activity in vitro, and no anti-vascular effects in vivo. These results endorse the current theories concerning two independent actions exerted by DMXAA.

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January 2009
Volume 34 Issue 1

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Barbera M, Kettunen MI, Caputo A, Hu D, Gobbi S, Brindle KM and Carrara M: Immune-modulating and anti-vascular activities of two xanthenone acetic acid analogues: A comparative study to DMXAA. Int J Oncol 34: 273-279, 2009
APA
Barbera, M., Kettunen, M.I., Caputo, A., Hu, D., Gobbi, S., Brindle, K.M., & Carrara, M. (2009). Immune-modulating and anti-vascular activities of two xanthenone acetic acid analogues: A comparative study to DMXAA. International Journal of Oncology, 34, 273-279. https://doi.org/10.3892/ijo_00000149
MLA
Barbera, M., Kettunen, M. I., Caputo, A., Hu, D., Gobbi, S., Brindle, K. M., Carrara, M."Immune-modulating and anti-vascular activities of two xanthenone acetic acid analogues: A comparative study to DMXAA". International Journal of Oncology 34.1 (2009): 273-279.
Chicago
Barbera, M., Kettunen, M. I., Caputo, A., Hu, D., Gobbi, S., Brindle, K. M., Carrara, M."Immune-modulating and anti-vascular activities of two xanthenone acetic acid analogues: A comparative study to DMXAA". International Journal of Oncology 34, no. 1 (2009): 273-279. https://doi.org/10.3892/ijo_00000149