Lazarus H, Raso V, Samy T S
Cancer Res. 1977 Oct;37(10):3731-6.
Neocarzinostatin (NCS) is an acidic protein (molecular weight, 10,700) isolated from Streptomyces carzinostaticus that has antitumor activity both in model rodent systems and in humans. In vitro it inhibits the growth of a human lymphoblastic leukemic cell line (CCRF-CEM) at a very low concentration (the amount of drug that causes a 50% inhibition of growth compared to control cultures as extrapolated from a dose-response curve (ID50), 2.4 X 10(-9) M). We covalently coupled NCS to the N-hydroxysuccinimide ester of agarose and obtained a product that, by a variety of biochemical and immunological criteria, has been demonstrated to be devoid of any free or loosely bound NCS. Agarose-bound NCS, which is unable to enter cells because of its size, retains a significant amount of inhibitory activity (ID50, 6 to 15 X 10(-9) M) and is also capable of inhibiting tritiated deoxythymidine incorporation into CCRF-CEM cells. Since agarose-bound NCS cannot enter mammalian cells, the above findings indicate that NCS is able to exert its toxic effects by binding to or reacting with receptors on the cell membrane.
新制癌菌素（NCS）是一种从制癌链霉菌中分离出的酸性蛋白质（分子量为10,700），在啮齿动物模型系统和人类中均具有抗肿瘤活性。在体外，它能在极低浓度下抑制人淋巴细胞白血病细胞系（CCRF-CEM）的生长（根据剂量反应曲线外推得出，与对照培养物相比，导致生长抑制50%的药物量（ID50）为2.4×10⁻⁹ M）。我们将NCS与琼脂糖的N-羟基琥珀酰亚胺酯共价偶联，得到了一种产物，通过各种生化和免疫学标准证明其不含任何游离或松散结合的NCS。由于琼脂糖结合的NCS因其大小而无法进入细胞，但仍保留大量抑制活性（ID50为6至15×10⁻⁹ M），并且还能够抑制氚标记的脱氧胸苷掺入CCRF-CEM细胞。由于琼脂糖结合的NCS不能进入哺乳动物细胞，上述发现表明NCS能够通过与细胞膜上的受体结合或反应来发挥其毒性作用。
