Actinonin, a peptidomimetic antibiotic that inhibits HsPDF(human peptide deformylase), also inhibits the proliferation of 16 human cancer cell lines. Actinonin inhibits cell growth in various human tumor cell lines. The IC50 of 4, 6.9, 12.8, 16.6, 27.4, 15.7 and 49.3 μM for Raji cells, MDA-MB-468 cells,PC3 cells, SK-LC-19 cells, Hela cells, HT-1080 cells and AL67 cells, respectively.. In animal models, oral or parenteral actinonin was well tolerated and inhibited human prostate cancer and lung cancer growth. Actinonin has been safely administered to mice as an antibiotic at doses up to 400 mg/kg. Actinonin does not appear to have significant toxicity to normal tissues, despite its antitumor activity in vitro. Remarkably, Actinonin exhibits significant antitumor activity when given i.p. or orally in a CWR22 human prostate tumor xenograft model in nude mice. During treatment, the animals show no signs of toxicity[2]. Actinonin which has been found to be an inhibitor of aminopeptidase M (EC 3.4.11.2) also inhibited enkephalinase A (EC 3.4.24.11) and enkephalin aminopeptidase which were partially purified from the corpus striatum membrane of guinea-pig brain. The IC50 values were 5.6 microM for enkephalinase A and 0.39 microM for enkephalin aminopeptidase. The analgesic effect of [Met5]enkephalin injected intracisternally (i.cist., 50 micrograms) was potentiated by an intraperitoneal (i.p., 100 and 300 mg/kg) as well as an i.cist. (25 micrograms) injection of actinonin. Actinonin was found to inhibit all three enzymes of enkephalin metabolism and, when given peripherally, to potentiate enkephalin analgesia[3]. Anti-VaPDF (V. anguillarum PDF) and anti-V. anguillarum activities of actinonin were dose-dependent, and the IC50 values were 6.94 and 2.85 μM, respectively[4].
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