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British Journal of Cancer logoLink to British Journal of Cancer
. 1991 Apr;63(4):541–545. doi: 10.1038/bjc.1991.127

The relationship between tissue levels of flavone acetic acid (NSC 347512) and site dependent anti-tumour activity in murine colon tumours.

M C Bibby 1, R M Phillips 1, J A Double 1
PMCID: PMC1972360  PMID: 2021538

Abstract

Flavone acetic acid (FAA) is extremely active against subcutaneous transplantable tumours in mice, but disappointingly there has been no demonstrable clinical activity. Previous studies have shown that lung tumour deposits are less responsive than the same cells implanted subcutaneously. The aim of this study is to examine the tissue disposition of FAA in an attempt to explain this site-dependent activity. The data show clearly that FAA clearance curves are influenced by the presence of MAC 15A tumours growing either subcutaneously or systemically. The decreased clearance of FAA from MAC 15A tumour bearing animals does not however explain the resistance of lung deposits. Neither can this be explained by differences in metabolism in these different sites. Cytotoxic metabolites have not been detected either in vitro or in vivo and their role in the mechanism of action of FAA is questionable.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bibby M. C., Double J. A., Ali S. A., Fearon K. C., Brennan R. A., Tisdale M. J. Characterization of a transplantable adenocarcinoma of the mouse colon producing cachexia in recipient animals. J Natl Cancer Inst. 1987 Mar;78(3):539–546. [PubMed] [Google Scholar]
  2. Bibby M. C., Double J. A., Loadman P. M., Duke C. V. Reduction of tumor blood flow by flavone acetic acid: a possible component of therapy. J Natl Cancer Inst. 1989 Feb 1;81(3):216–220. doi: 10.1093/jnci/81.3.216. [DOI] [PubMed] [Google Scholar]
  3. Bibby M. C., Double J. A., Loadman P. M. Unique chemosensitivity of MAC 16 tumours to flavone acetic acid (LM975, NSC 347512). Br J Cancer. 1988 Sep;58(3):341–344. doi: 10.1038/bjc.1988.215. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Chabot G. G., Bissery M. C., Corbett T. H., Rutkowski K., Baker L. H. Pharmacodynamics and causes of dose-dependent pharmacokinetics of flavone-8-acetic acid (LM-975; NSC-347512) in mice. Cancer Chemother Pharmacol. 1989;24(1):15–22. doi: 10.1007/BF00254099. [DOI] [PubMed] [Google Scholar]
  5. Chabot G. G., Bissery M. C., Gouyette A. Flavone acetic acid (LM-975; NSC-347512) activation to cytotoxic species in vivo and in vitro. Cancer Chemother Pharmacol. 1989;24(5):273–276. doi: 10.1007/BF00304757. [DOI] [PubMed] [Google Scholar]
  6. Corbett T. H., Bissery M. C., Wozniak A., Plowman J., Polin L., Tapazoglou E., Dieckman J., Valeriote F. Activity of flavone acetic acid (NSC-347512) against solid tumors of mice. Invest New Drugs. 1986;4(3):207–220. doi: 10.1007/BF00179586. [DOI] [PubMed] [Google Scholar]
  7. Cummings J., Double J. A., Bibby M. C., Farmer P., Evans S., Kerr D. J., Kaye S. B., Smyth J. F. Characterization of the major metabolites of flavone acetic acid and comparison of their disposition in humans and mice. Cancer Res. 1989 Jul 1;49(13):3587–3593. [PubMed] [Google Scholar]
  8. Damia G., Zanette M. L., Rossi C., Mandelli R., Ferrari A., D'Incalci M. Dose-dependent pharmacokinetics of flavone acetic acid in mice. Cancer Chemother Pharmacol. 1988;22(1):47–50. doi: 10.1007/BF00254180. [DOI] [PubMed] [Google Scholar]
  9. Donelli M. G., D'Incalci M., Garattini S. Pharmacokinetic studies of anticancer drugs in tumor-bearing animals. Cancer Treat Rep. 1984 Feb;68(2):381–400. [PubMed] [Google Scholar]
  10. Double J. A., Ball C. R., Cowen P. N. Transplantation of adenocarcinomas of the colon in mice. J Natl Cancer Inst. 1975 Jan;54(1):271–275. doi: 10.1093/jnci/54.1.271. [DOI] [PubMed] [Google Scholar]
  11. Double J. A., Bibby M. C., Loadman P. M. Pharmacokinetics and anti-tumour activity of LM985 in mice bearing transplantable adenocarcinomas of the colon. Br J Cancer. 1986 Oct;54(4):595–600. doi: 10.1038/bjc.1986.214. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Giavazzi R., Garofalo A., Damia G., Garattini S., D'Incalci M. Response to flavone acetic acid (NSC 347512) of primary and metastatic human colorectal carcinoma xenografts. Br J Cancer. 1988 Mar;57(3):277–280. doi: 10.1038/bjc.1988.59. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Kerr D. J., Kaye S. B., Cassidy J., Bradley C., Rankin E. M., Adams L., Setanoians A., Young T., Forrest G., Soukop M. Phase I and pharmacokinetic study of flavone acetic acid. Cancer Res. 1987 Dec 15;47(24 Pt 1):6776–6781. [PubMed] [Google Scholar]
  14. Kerr D. J., Maughan T., Newlands E., Rustin G., Bleehen N. M., Lewis C., Kaye S. B. Phase II trials of flavone acetic acid in advanced malignant melanoma and colorectal carcinoma. Br J Cancer. 1989 Jul;60(1):104–106. doi: 10.1038/bjc.1989.230. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Plowman J., Narayanan V. L., Dykes D., Szarvasi E., Briet P., Yoder O. C., Paull K. D. Flavone acetic acid: a novel agent with preclinical antitumor activity against colon adenocarcinoma 38 in mice. Cancer Treat Rep. 1986 May;70(5):631–635. [PubMed] [Google Scholar]
  16. Zaharko D. S., Grieshaber C. K., Plowman J., Cradock J. C. Therapeutic and pharmacokinetic relationships of flavone acetic acid: an agent with activity against solid tumors. Cancer Treat Rep. 1986 Dec;70(12):1415–1421. [PubMed] [Google Scholar]
  17. Zwi L. J., Baguley B. C., Gavin J. B., Wilson W. R. Blood flow failure as a major determinant in the antitumor action of flavone acetic acid. J Natl Cancer Inst. 1989 Jul 5;81(13):1005–1013. doi: 10.1093/jnci/81.13.1005. [DOI] [PubMed] [Google Scholar]

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