Biopolymers from Marine Invertebrates: XI: 1) Characterization of an Antineoplastic Glycoprotein, Dolabellanin A, from the Albumen Gland of a Sea Hare, Dolabella auricularia

Abstract

An anti-neoplastic factor, dolabellanin A, inducing tumor lysis was purified from the albumen gland of a sea hare, Dolabella auricularia. Purified dolabellanin A was found to be a glycoprotein of 250 kilodaltons containing 4 subunits. This factor was half-maximally active towords a variety of tumor cells at 1-18 ng protein/ml and lysed tumor necrosis factor (TNF)-resistant tumor cells. Dolabellanin A was labile on heating, at low and high pH, and on treatment with urea, guanidine, sodium lauryl sulfate or trypsin, but not with 2-mercaptoethanol or periodate. Dolabellanin A completely inhibited the syntheses of deoxyribonucleic acid and ribonucleic acid by tumor cells within 1 h and caused their complete cytolysis within 18 h. Tumor lysis by dolabellanin A was not inhibited by anti-TNF antibody but was inhibited by certain sugars, suggesting that recognition of a sugar moiety is a key step in its induction of cytolysis.Dolabellanin A also prolonged the survival of mice bearing syngneic MM46 ascitic tumors (p<0.001). These results suggest that dolabellanin A, found in an invertebrate, the sea hare, is a new antitumor factor. © 1989, The Pharmaceutical Society of Japan. All rights reserved.