Effects of Combretastatin A-4 prodrug against a panel of malignant human B-lymphoid cell lines
Effects of Combretastatin A-4 prodrug against a panel of malignant human B-lymphoid cell lines
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DOI：
10.1097/00001813-200006000-00009
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发表时间：
2000-06-01
影响因子：
2.3
通讯作者：
Al-Katib, AM
中科院分区：
文献类型：
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作者：
Nabha, SM;Wall, NR;Al-Katib, AM
Combretastatin A-4（CA-4）是从南非杨柳Combretum caffrom中分离的化合物家族之一，CA-4被发现对小鼠黑色素瘤和多种其它人类实体瘤具有活性。我们首次报道了CA-4对一组恶性人B淋巴细胞系[早期前B急性淋巴细胞白血病（Reh）、弥漫性大细胞淋巴瘤（WSU-DLCL 2）、慢性淋巴细胞白血病（WSU-CLL）和瓦尔登斯特伦巨球蛋白血症（WSU-WM）]的作用。我们的结果表明，使用CA-4的前药形式，在所有测试的细胞系中的浓度依赖性生长抑制，尽管WSU-DLCL 2更敏感。暴露于4 nM CA-4 96 h诱导Reh中77%的生长抑制，WSU-CLL中86%的生长抑制和WSU-WM中92%的生长抑制。当针对WSU-DLCL 2细胞系使用时，CA-4的该游戏浓度是完全有毒的。形态学检查显示CA-4诱导形成巨大的多核细胞，这是有丝分裂灾难中常见的现象。仅检测到极少量显示凋亡特征的细胞。在WSU-DLCL 2细胞中，CA-4（3 nM）在48 h后诱导最高的凋亡（5%），而死亡细胞的百分比约为47%。用流式细胞术测定，5 nM CA-4分别使Reh、WSU-CLL、WSU-WM和WSU-DLCL 2细胞暴露24 h，诱导19、28、57和75%的G（2）/M阻滞。基于这些初步研究，我们认为有丝分裂灾难是CA-4诱导细胞死亡而不是细胞凋亡的主要机制。我们实验室目前正在研究进一步研究以阐明CA-4体外和体内活性的机制[（C）2000 Lippincott威廉姆斯& Wilkins.]。
Combretastatin A-4 (CA-4) is one of a family of compounds isolated from the South African willow tree Combretum caffrom, CA-4 was found to be active against murine melanoma and a variety of other human solid tumors. For the first time, we report the effect of CA-4 against a panel of malignant human B-lymphoid cell lines [early pre-B acute lymphoblastic leukemia (Reh), diffuse large cell lymphoma (WSU-DLCL2), chronic lymphocytic leukemia (WSU-CLL) and Waldenstrom's macroglobulinemia (WSU-WM)]. Our results indicate, using the prodrug form of CA-4, a concentration-dependent growth inhibition in all tested cell lines, although WSU-DLCL2 was more sensitive. Exposure to 4 nM CA-4 for 96 h induced 77% growth inhibition in Reh, 86% in WSU-CLL and 92% in WSU-WM. When used against the WSU-DLCL2 cell line, this game concentration of CA-4 was completely toxic. Morphological examination showed CA-4 induced the formation of giant, multinucleated cells, a phenomenon commonly found In mitotic catastrophe. Only minimal numbers of cells showing characteristics of apoptosis were detected. In WSU-DLCL2 cells, CA-4 (3 nM) induced the highest apoptosis (5%) after 48 h, while the percentage of dead cells was approximately 47%. Exposure of Reh, WSU-CLL, WSU-WM and WSU-DLCL2 cells for 24 h to 5 nM CA-4 induced 19, 28, 57 and 75% G(2)/M arrest, as determined by flow cytometry, respectively. Based on these preliminary studies, we believe that mitotic catastrophe is the predominant mechanism by which CA-4 induces cell death rather than apoptosis, Further studies to elucidate the mechanisms of CA-4 activity in vitro and in vivo are currently under investigation in our laboratory, [(C) 2000 Lippincott Williams & Wilkins.].