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Activity of flavone acetic acid (NSC-347512) against solid tumors of mice

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Abstract

Flavone acetic acid (FAA) is a new antitumor agent that has recently entered Phase I clinical trials. In preclinical studies, we have found that FAA was broadly active against a variety of transplantable solid tumors of mice (colon #51, #07, #10, #26; pancreatic ductal adenocarcinomas #02 and #03; mammary adenocarcinoma #16/C/Adr; M5076 reticulum cell sarcoma and Glasgow's osteosarcoma). FAA was curative for colon adenocarcinoma # 10 and pancreatic ductal adenocarcinoma # 03. Thus, for the first time an agent has been identified with very broad, perhaps nearly universal solid tumor activity. FAA was also found to be orally active and stable in solution at 37 °C for 48 h. FAA was selectively cytotoxic in vitro for solid tumors over leukemias L1210 and P388 (in a soft-agar colony formation assay), thus correlating cellular selectivity in vitro with in vivo antitumor activity. The finding that FAA was active in vitro, established that the agent did not need metabolism (activation) outside the tumor cell. The main drawback of FAA was an unusual ‘threshold’ behavior in which only a narrow range of doses were active and splitting the dose markedly decreased activity.

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Authors and Affiliations

  1. Division of Oncology, Dept. of Medicine, Wayne State University School of Medicine, Detroit, MI, USA

    Thomas H. Corbett, Marie-Christine Bissery, Lisa Polin, Efstathios Tapazoglou, Julia Dieckman & Frederick Valeriote

  2. Veterans Administration Medical Center, Allen Park, MI, USA

    Antoinette Wozniak

  3. Developmental Therapeutics Program, Division of Cancer Treatment, National Cancer Institute, 20892, Bethesda, MD, USA

    Jacqueline Plowman

Authors
  1. Thomas H. Corbett
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  2. Marie-Christine Bissery
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  3. Antoinette Wozniak
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  4. Jacqueline Plowman
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  5. Lisa Polin
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  6. Efstathios Tapazoglou
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  7. Julia Dieckman
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  8. Frederick Valeriote
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Corbett, T.H., Bissery, MC., Wozniak, A. et al. Activity of flavone acetic acid (NSC-347512) against solid tumors of mice. Invest New Drugs 4, 207–220 (1986). https://doi.org/10.1007/BF00179586

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