Hu Z B, Gignac S M, Quentmeier H, Pettit G R, Drexler H G
DSM-German Collection of Microorganisms and Cell Cultures, Department of Human and Animal Cell Cultures, Braunschweig.
Leuk Res. 1993 Apr;17(4):333-9. doi: 10.1016/0145-2126(93)90020-l.
Dolastatins are naturally occurring peptides isolated from marine animals and are known to be potent anti-neoplastic agents. Here, the three compounds dolastatin 10 (Dola 10), dolastatin 15 (Dola 15) and deo-dolastatin 10 (Deo-Dola 10) were added to cultures of two human chronic B-leukemia cell lines, JVM-2 and EHEB. The three dolastatins (Dola 10 > Dola 15 > Deo-Dola 10) inhibited cell proliferation and immunoglobulin production. Decreased cell growth and lack of accumulation of immunoglobulin was not caused by cytotoxicity as cell viability in the cultures remained high. The unchanged surface marker immunoprofiles during treatment and a predominance of treated cells in S and G2/M phase suggested cytostatic rather than directly cytotoxic effects. Exposure to these reagents increased quickly, albeit only short c-myc and bcl-2 mRNA expression. These results indicate that the three dolastatins are potent inhibitors of leukemic B-cell proliferation.
多拉司他汀是从海洋动物中分离出的天然存在的肽，已知是有效的抗肿瘤剂。在此，将三种化合物多拉司他汀10（Dola 10）、多拉司他汀15（Dola 15）和去氧多拉司他汀10（Deo-Dola 10）添加到两种人类慢性B淋巴细胞白血病细胞系JVM-2和EHEB的培养物中。这三种多拉司他汀（Dola 10 > Dola 15 > Deo-Dola 10）抑制细胞增殖和免疫球蛋白产生。细胞生长的降低和免疫球蛋白积累的缺乏并非由细胞毒性引起，因为培养物中的细胞活力仍然很高。治疗期间表面标志物免疫谱未改变，且处于S期和G2/M期的处理细胞占优势，提示其为细胞生长抑制作用而非直接细胞毒性作用。暴露于这些试剂后，c-myc和bcl-2 mRNA表达迅速增加，尽管只是短暂增加。这些结果表明这三种多拉司他汀是白血病B细胞增殖的有效抑制剂。
