VRCTC-310--a novel compound of purified animal toxins separates antitumor efficacy from neurotoxicity.
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 cytotoxicity in vitro and which has demonstrated interesting in vivo antitumor efficacy.
Newman
R A
RA
Department of Clinical Investigation, University of Texas M.D. Anderson Cancer Center, Houston.
Vidal
J C
JC
Viskatis
L J
LJ
Johnson
J
J
Etcheverry
M A
MA
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000633:toxicity*; D004179:Cobra Cardiotoxin Proteins / Q000494:pharmacology* / Q000633:toxicity*; D003435:Crotalid Venoms / Q000494:pharmacology / Q000633:toxicity; D003439:Crotoxin / Q000494:pharmacology* / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004361:Drug Tolerance; D008175:Lung Neoplasms / Q000188:drug therapy; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D009422:Nervous System Diseases / Q000139:chemically induced*; D009498:Neurotoxins / Q000494:pharmacology* / Q000633:toxicity*
D000970:Antineoplastic Agents; D004179:Cobra Cardiotoxin Proteins; D003435:Crotalid Venoms; D004338:Drug Combinations; D009498:Neurotoxins; C084936:cardiotoxin, crotoxin drug combination; D003439:Crotoxin