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Induction of Plasminogen Activator in Cultured Cells by Macrocyclic Plant Diterpene Esters and Other Agents Related to Tumor Promotion

机译:大环植物二萜酯和其他与肿瘤促进有关的药物诱导培养细胞中的纤溶酶原激活剂

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摘要

In vitro systems that are responsive to tumor-promoting agents may facilitate the identification of such agents and the analysis of their mode of action. We have previously reported that the potent tumor promoter phorbol-12-myristate-13-acetate induces the synthesis of the enzyme plasminogen activator in cultured chick embryo fibroblasts. We have, therefore, tested various compounds for their ability to induce plasminogen activator in chicken embryo fibroblasts. Among these, phorbol esters and other macrocyclic diterpene esters isolated from species of the families Euphorbiaceae and Thymelaeaceae were potent inducers of plasminogen activator. These compounds maximally induced enzyme to the same levels, although they differed in their relative molar potencies. Structural requirements for in vitro activity paralleled the requirements for activity in vivo. These results indicate that induction of plasminogen activator is a useful marker for the biologically active macrocyclic diterpene esters. On the other hand, tumor-promoting agents such as anthralin, cantharidin, Tween 60, and tobacco leaf extract failed to induce plasminogen activator.
机译:对肿瘤促进剂有反应的体外系统可以促进这类药物的鉴定和其作用方式的分析。我们以前曾报道过,有效的肿瘤启动子phorbol-12-肉豆蔻酸酯-13-乙酸酯可诱导培养的鸡胚成纤维细胞中酶纤溶酶原激活剂的合成。因此,我们已经测试了各种化合物在鸡胚成纤维细胞中诱导纤溶酶原激活剂的能力。其中,从大戟科和百里香科中分离出的佛波酯和其他大环二萜酯是纤溶酶原激活剂的有效诱导剂。这些化合物最大程度地诱导了相同水平的酶,尽管它们的相对摩尔效能不同。体外活性的结构要求与体内活性的要求平行。这些结果表明,纤溶酶原激活剂的诱导是生物活性大环二萜酯的有用标记。另一方面,肿瘤促发剂,如蒽林,邻苯二酚,吐温60和烟叶提取物未能诱导纤溶酶原激活剂。

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