Gebbia V, Citarrella P, Miserendino V, Valenza R, Borsellino N, Pesta A, Pettit R, May S
Section of Oncology, University of Palermo, Italy.
Tumori. 1992 Jun 30;78(3):167-71. doi: 10.1177/030089169207800304.
The macrocyclic lactone bryostatin-1 was found to exert in vitro antineoplastic activity against several leukemic cell lines, including human K562 erythroleukemia, HL60 promyelocytic leukemia, REH and MOLT-4 lymphoblastic leukemias, CCRF-CEM lymphoma, KG-1 myeloid leukemia, and murine P388 lymphocytic leukemia. No statistically significant difference in sensitivity to bryostatin-1 was found between adriamycin-resistant P388 and K526 subclones and their sensitive counterparts. Freshly explanted clonogenic leukemic cells showed a variable sensitivity to bryostatin-1 in 10/12 tested samples. The IC50 of clonogenic leukemic cells was 4 x 10(-3) M bryostatin-1, and that of normal marrow CFU-GM was 10(-5) M. Leukemic cells exposed to bryostatin-1 showed a variable degree of monocytic differentiation as evaluated by ANAE staining and morphology. Bryostatin-1 is also able to inhibit the growth of CFU-GM from myelodysplastic marrow and to shorten the duration of dysplastic hematopoiesis in liquid culture. In conclusion, these data suggest that bryostatin-1 is a potent antileukemic agent in vitro that may be potentially useful for clinical studies.
大环内酯类苔藓抑素-1被发现对多种白血病细胞系具有体外抗肿瘤活性，包括人K562红白血病、HL60早幼粒细胞白血病、REH和MOLT-4淋巴细胞白血病、CCRF-CEM淋巴瘤、KG-1髓性白血病以及鼠P388淋巴细胞白血病。对阿霉素耐药的P388和K526亚克隆与其敏感对应物之间对苔藓抑素-1的敏感性未发现统计学上的显著差异。新鲜分离的克隆形成性白血病细胞在12个测试样本中的10个中对苔藓抑素-1表现出可变的敏感性。克隆形成性白血病细胞的IC50为4×10⁻³ M苔藓抑素-1，而正常骨髓CFU-GM的IC50为10⁻⁵ M。通过ANAE染色和形态学评估，暴露于苔藓抑素-1的白血病细胞表现出不同程度的单核细胞分化。苔藓抑素-1还能够抑制骨髓增生异常综合征骨髓中CFU-GM的生长，并缩短液体培养中发育异常造血的持续时间。总之，这些数据表明苔藓抑素-1在体外是一种有效的抗白血病药物，可能对临床研究有潜在用途。
