fostriecin and Colonic-Neoplasms

Advanced subcutaneous Colon 38 tumours in mice were used for the assessment of activity of a number of anticancer drugs. Activity was measured by histological examination of tumours 24 h after a single dose of the drug and in some cases by tumour growth delay. Agents thought to exert their cytotoxic effect by damaging DNA, including Adriamycin, amsacrine and its analogue CI-921, cyclophosphamide, 5-fluorouracil and methotrexate produced no gross histological changes after 24 h, even though some delayed the growth of subcutaneous tumours. In contrast, flavone acetic acid, fostriecin and homoharringtonine caused extensive necrosis of tumours after 24 h, and each delayed the growth of advanced subcutaneous tumours by at least 10 days when administered as a single dose. The histological effects of flavone acetic acid and fostriecin were indistinguishable from those of recombinant human tumour necrosis factor alpha. It is proposed that histological assay of advanced tumours may provide a useful adjunct to existing methods in screening for antitumour agents with novel mechanisms of action.

Topics: Alkaloids; Alkenes; Animals; Antibiotics, Antineoplastic; Antineoplastic Agents; Colonic Neoplasms; Drug Screening Assays, Antitumor; Flavonoids; Harringtonines; Homoharringtonine; Mice; Mice, Inbred Strains; Polyenes; Pyrones; Tumor Necrosis Factor-alpha