Preclinical in vitro and in vivo activity of 5,6-dimethylxanthenone-4-acetic acid (original) (raw)

British Journal of Cancer volume 71, pages 1204–1209 (1995)Cite this article

Abstract

5,6-Dimethylxanthenone-4-acetic acid (5,6-MeXAA) is a fused tricyclic analogue of flavone acetic acid (FAA) which was developed in an attempt to improve on the activity of FAA. Previous studies have shown 5,6-MeXAA to be curative in 80% of mice bearing colon 38 tumours and 12 times more dose potent than FAA. This investigation has demonstrated that a murine colon tumour cell line (MAC15A) is approximately 60 times more sensitive to 5,6-MeXAA than to FAA, although these differences were not seen in three human cell lines tested. 5,6-MeXAA caused significant blood flow shutdown and haemorrhagic necrosis in subcutaneous MAC15A tumours in syngeneic and nude hosts, but measurable changes in tumour volume were seen only in syngeneic hosts. 5,6-MeXAA was inactive against intraperitoneal MAC15A but produced significant anti-tumour effects against the same cell line inoculated via an intravenous route. FAA has been shown previously to be inactive in this model. Interestingly, the effects against lung colonies were not accompanied by obvious necrotic changes, suggesting that they may be the result of increased direct cytotoxicity rather than an indirect host mechanism. Further studies to investigate the effects against systemic tumour deposits are under way.

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Authors and Affiliations

  1. Clinical Oncology Unit, University of Bradford, UK
    AL Laws

Authors

  1. AL Laws
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  2. AM Matthew
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  3. JA Double
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  4. MC Bibby
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Laws, A., Matthew, A., Double, J. et al. Preclinical in vitro and in vivo activity of 5,6-dimethylxanthenone-4-acetic acid.Br J Cancer 71, 1204–1209 (1995). https://doi.org/10.1038/bjc.1995.234

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