Natural Products Research Institute, College of Pharmacy, Seoul National University, 599 Gwanangno, Gwanak-gu, Seoul 151-742, Korea.
J Cell Biochem. 2010 Aug 1;110(5):1272-8. doi: 10.1002/jcb.22643.
Acharan sulfate (AS), isolated from the giant African snail Achatina fulica, is a novel glycosaminoglycan, consisting primarily of the repeating disaccharide structure alpha-D-N-acetylglucosaminyl (1 --> 4) 2-sulfoiduronic acid. AS shows anti-tumor activity in vitro and in vivo. Despite this activity, AS is only weakly cytotoxic towards cancer cells. We examine the interactions between AS and cell-surface proteins in an effort to explain this anti-tumor activity. Using flow cytometry and affinity column chromatography, we confirm that AS has strong affinity to specific cell-surface proteins including nucleolin (NL) in A549 human lung adenocarcinomas. Surprisingly, we found the translocation of NL from nucleus to cytoplasm under the stimulation of AS (100 microg/ml) in vitro. Also, as NL exits the nucleus, the levels of growth factors such as bFGF and signaling cascade proteins, such as p38, p53, and pERK, are altered. These results suggest that the communication between AS and NL plays a critical role on signal transduction in tumor inhibition.
硫酸乙酰肝素（AS）是从巨型非洲蜗牛 Achatina fulica 中分离出来的一种新型糖胺聚糖，主要由重复的二糖结构 α-D-N-乙酰氨基葡萄糖（1-->4）2-磺基二糖组成。AS 在体外和体内均表现出抗肿瘤活性。尽管具有这种活性，但 AS 对癌细胞的细胞毒性较弱。我们研究了 AS 与细胞表面蛋白之间的相互作用，以解释这种抗肿瘤活性。通过流式细胞术和亲和柱层析，我们证实 AS 与包括 A549 人肺腺癌细胞中的核仁素（NL）在内的特定细胞表面蛋白具有很强的亲和力。令人惊讶的是，我们发现 AS（100μg/ml）刺激下 NL 从核内易位到细胞质。此外，随着 NL 从核内输出，生长因子（如 bFGF）和信号级联蛋白（如 p38、p53 和 pERK）的水平发生改变。这些结果表明，AS 和 NL 之间的通讯在肿瘤抑制中的信号转导中起着关键作用。
