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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Investigational new drugs 11 (1993), S. 11-15 
    ISSN: 1573-0646
    Keywords: crotoxin ; cytotoxicity ; erythroleukemia ; phospholipase A2 ; neurotoxin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The cytotoxic effect of crotoxin, a heterodimeric phospholipase A2 from the venom ofCrotalus durissus terrificus, was examined on murine erythroleukemia cellsin vitro. Crotoxin cytocidal effect on cell growth had an EC50 of approximately 0.1–0.2 μM (3.0–5.0 μg/ml) in serum-free medium. Cytotoxicity was independent of cell growth since both quiescent and proliferating cells had similar sensitivities to the toxin. Dissociation of the crotoxin complex and phospholipase A2 activity of its subunit B are required for cytotoxicity, since the covalently linked crotoxin complex or the specific alkylation of the active site on the subunit B abolish the cytotoxic activity on murine erythroleukemia cells. Specific interaction between crotoxin and murine erythroleukemia cells appears to be required since the homologous phospholipase A2 fromCrotalus atrox venom, with a higher phospholipase A2 specific activity than crotoxin, was 86-fold less potent than crotoxin. The data in this report show that the cytotoxic effect of crotoxin on murine erythroleukemia cells is consistent with the specific binding of the toxin resulting in cytocidal action mediated by the phospholipase A2 activity of crotoxin subunit B.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1573-0646
    Keywords: VRCTC-310 ; animal venom ; phospholipase A2 ; cardiotoxin ; crotoxin ; Lewis lung carcinoma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Two purified animal venom toxins, crotoxin and cardiotoxin, have been combined to produce a unique natural product (VRCTC-310) currently under investigation as an antitumor agent by the National Cancer Institute.In vitro, it has demonstrated cytotoxic disease specificity and a unique mechanism of action when submitted to COMPARE analysis.In vivo, tolerance was developed to the neurotoxic properties of crotoxin which allowed comparison of several schedules of fixed and escalating daily i.m. doses to mice bearing s.c. Lewis Lung carcinoma. An 83% inhibition of tumor growth was achieved using an escalating dose schedule starting at 1.8 mg/kg and reaching 6.3 mg/kg/day on day 20. Although some irritation around the sites of i.m. injection was noted, animal weight loss was negligible and there were no other signs of adverse toxicity. This natural product represents a new, membrane interactive anticancer agent which produces a unique spectrum of cytotoxicityin vitro and which has demonstrated interestingin vivo antitumor efficacy.
    Type of Medium: Electronic Resource
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