A marine natural product, patellamide D, reverses multidrug resistance in a human leukemic cell line.
A cyclic octapeptide (patellamide D) isolated from the marine tunicate, Lissaclinum patella, acts as a resistance-modifying agent in the multidrug resistant CEM/VLB100 human leukemic cell line. A three-day microculture tetrazolium proliferation assay was used to determine the 50% inhibitory concentration (IC50) for vinblastine, colchicine and adriamycin and calculate the degree of resistance modulation. Patellamide D at 3.3 microM was compared with 5.1 microM verapamil in modulating drug resistance in vitro. The IC50 for vinblastine was reduced from 100 ng/ml to 1.5 ng/ml in the presence of patellamide D or to 2.1 ng/ml when exposed to verapamil. Colchicine cytotoxicity was enhanced only 1.4-fold by verapamil, as compared with 2.8-fold using patellamide D (IC50 was reduced from 140 ng/ml to 100 ng/ml or 50 ng/ml). Adriamycin toxicity was reduced from IC50 > 1000 ng/ml to 110 ng/ml and 160 ng/ml when coexposed to patellamide D and verapamil, respectively. Our results indicate that patellamide D acts as a selective antagonist in multidrug resistance and stresses the importance of investigating marine-derived compounds as a potential new source for modulators of the drug-resistance phenotype.
Williams
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Department of Biological Sciences, University of California, Santa Barbara 93106.
Jacobs
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D000595:Amino Acid Sequence; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line / Q000187:drug effects; D004351:Drug Resistance; D006801:Humans; D007448:Invertebrates / Q000737:chemistry; D007938:Leukemia; D008969:Molecular Sequence Data; D010456:Peptides, Cyclic / Q000302:isolation & purification / Q000494:pharmacology*; D014700:Verapamil / Q000494:pharmacology
D000970:Antineoplastic Agents; D010456:Peptides, Cyclic; C059972:patellamide D; D014700:Verapamil