Yamazaki M, Kisugi J, Iijima R
Dept. of Medical Chemistry, Faculty of Pharmaceutical Sciences, Teikyo University.
Gan To Kagaku Ryoho. 1997 Sep;24(11):1477-85.
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.
我们在海洋无脊椎动物中寻找新的宿主防御分子。我们在节肢动物和软体动物中发现了几种新的细胞溶解因子。特别是,发现海兔具有强大的抗肿瘤糖蛋白。这些新型糖蛋白从黑指纹海兔和耳状芋螺中纯化至表观同质,分别命名为海兔素和芋螺素。分离出的糖蛋白能裂解所有测试的肿瘤细胞,包括对肿瘤坏死因子有抗性的细胞,但不会裂解正常的白细胞和红细胞。这些糖蛋白在2小时内完全抑制肿瘤细胞的DNA和RNA合成,并在18小时内导致肿瘤裂解。N-乙酰神经氨酸的存在会抑制细胞溶解,这表明糖部分的识别是这些来自海兔的抗肿瘤糖蛋白导致肿瘤裂解的关键步骤。这些抗肿瘤因子,除了芋螺素C和P外,还具有抗菌活性。芋螺素A的N端部分序列与海兔素A和阿查辛相似。