Biopolymers from marine invertebrates. XI. Characterization of an antineoplastic glycoprotein, dolabellanin A, from the albumen gland of a sea hare, Dolabella auricularia.
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 towards 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 syngeneic MM46 ascitic tumors (p less than 0.001). These results suggest that dolabellanin A, found in an invertebrate, the sea hare, is a new antitumor factor.
Yamazaki
M
M
Kisugi
J
J
Kamiya
H
H
D000596:Amino Acids / Q000032:analysis; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D005088:Exocrine Glands / Q000378:metabolism*; D006023:Glycoproteins / Q000302:isolation & purification* / Q000494:pharmacology; D008974:Mollusca / Q000378:metabolism*; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000596:Amino Acids; D000970:Antineoplastic Agents; D006023:Glycoproteins; C063649:dolabellanin A protein, Dolabella auricularia