May W S, Sharkis S J, Esa A H, Gebbia V, Kraft A S, Pettit G R, Sensenbrenner L L
Johns Hopkins Oncology Center, Johns Hopkins University, Baltimore, MD 21205.
Proc Natl Acad Sci U S A. 1987 Dec;84(23):8483-7. doi: 10.1073/pnas.84.23.8483.
The bryostatins are macrocyclic lactones, extracted from the marine bryozoan Bugula neritina, and have been reported to be potent antineoplastic agents. Results described here demonstrate that the bryostatins may also be useful as stimulators of normal human hematopoietic cells since they can (i) directly stimulate bone marrow progenitor cells to form colonies in vitro and (ii) functionally activate neutrophils. Structure-activity studies with bryostatin congeners indicate that these stimulatory properties may be dependent on the chain length and the unsaturated nature of the acylated group at carbons 20 and 7 of the bryostatin molecule. These stimulatory properties demonstrate that the naturally occurring bryostatins can mimic many of the biological effects of multipotential granulocyte-macrophage colony-stimulating factor. Thus, the coupling of antineoplastic activity with stimulatory growth properties for normal hematopoietic cells makes this agent an excellent probe to dissect the mechanism(s) of normal hematopoiesis. In addition, bryostatin may represent a clinically attractive agent useful for treating bone marrow failure states.
苔藓抑素是从海洋苔藓虫类的美丽琥珀苔虫中提取的大环内酯类化合物，据报道是有效的抗肿瘤药物。此处描述的结果表明，苔藓抑素也可能作为正常人造血细胞的刺激剂，因为它们能够（i）在体外直接刺激骨髓祖细胞形成集落，以及（ii）功能性激活中性粒细胞。对苔藓抑素同系物的构效关系研究表明，这些刺激特性可能取决于苔藓抑素分子中第20位和第7位碳原子上酰基的链长和不饱和性质。这些刺激特性表明，天然存在的苔藓抑素可以模拟多能粒细胞-巨噬细胞集落刺激因子的许多生物学效应。因此，抗肿瘤活性与对正常造血细胞的刺激生长特性相结合，使该药物成为剖析正常造血机制的优秀探针。此外，苔藓抑素可能是一种临床上有吸引力的药物，可用于治疗骨髓衰竭状态。
