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[Antineoplastic glycoproteins in marine invertebrates]
M Yamazaki1, J Kisugi, R Iijima
1Dept. of Medical Chemistry, Faculty of Pharmaceutical Sciences, Teikyo University.
Abstract:
We searched marine invertebrates for new host defence molecules. We found several new cytolytic factors in Arthropoda and Mollusca. Especially, sea hares were revealed to have strong antitumor glycoproteins. These novel glycoproteins were purified to apparent homogeneity from Aplysia kurodai and Dolabella auricularia, and designated aplysianins and dolabellanins, respectively. The isolated glycoproteins lysed all the tumor cells tested, including TNF-resistant cells, but did not lyse normal white and red blood cells. The glycoproteins completely inhibited the synthesis of DNA and RNA by tumor cells within 2 hours and caused tumor lysis within 18 hours. Cytolysis was inhibited by the presence of N-acetylneuraminic acid, suggesting that the recognition of the sugar moiety is a key step in the tumor lysis by these antineoplastic glycoproteins from sea hares. These antitumor factors, except dolabellanins C and P, also showed anti-microbial activities. The sequence of the N-terminal part of dolabellanin A was similar to aplysianin A and achacin.