Cech P, Rosove M H, Harwig S S, Lehrer R I
Thromb Res. 1986 May 1;42(3):383-96. doi: 10.1016/0049-3848(86)90267-7.
Teleocidins are newly described indole alkaloid tumor promoters that are structurally distinct from phorbol diesters (PDE). We compared the effects of teleocidin and selected PDE on platelet aggregation, secretion and aspects of arachidonate metabolism. Three tumor-promoting PDE (phorbol myristate acetate (PMA), phorbol dibutyrate (PDBu) and 4-beta-phorbol didecanoate (4-beta-PDD] and a non-tumor promoting PDE (4-alpha-phorbol didecanoate (4-alpha-PDD] were used. Teleocidin and tumor promoting PDE caused platelet aggregation after a delay that was inversely related to tumor promoter concentration and also triggered secretion of alpha- and dense granules and selective release of lysosomal enzymes. Aggregation and its associated 125I-fibrinogen binding to platelets were both inhibited by Na2EDTA. 4-alpha-PDD was ineffective. Analysis of platelet aggregation responses and activation kinetics revealed that PDBu was 11.7 times less potent than teleocidin PMA, or 4-beta-PDD. Neither PDE nor teleocidin stimulated 14C-arachidonate release from normal human platelets, and both aggregated aspirin-treated platelets. These results show that representatives of two structurally distinct classes of tumor promoters, phorbol diesters and indole alkaloids, are potent activators of platelet aggregation, fibrinogen binding, and granule/lysosomal secretion, by a mechanism that bypasses arachidonate release and formation of cyclooxygenase-dependent arachidonate metabolites.
远侧霉素是新发现的吲哚生物碱肿瘤促进剂，其结构与佛波酯（PDE）不同。我们比较了远侧霉素和选定的佛波酯对血小板聚集、分泌及花生四烯酸代谢方面的影响。使用了三种促肿瘤的佛波酯（佛波醇肉豆蔻酸酯乙酸酯（PMA）、佛波醇二丁酸酯（PDBu）和4-β-佛波醇二癸酸酯（4-β-PDD））以及一种非促肿瘤的佛波酯（4-α-佛波醇二癸酸酯（4-α-PDD））。远侧霉素和促肿瘤的佛波酯在延迟后引起血小板聚集，延迟时间与肿瘤促进剂浓度呈负相关，还引发α颗粒和致密颗粒的分泌以及溶酶体酶的选择性释放。聚集及其相关的125I-纤维蛋白原与血小板的结合均被Na2EDTA抑制。4-α-PDD无效。对血小板聚集反应和激活动力学的分析表明，PDBu的效力比远侧霉素、PMA或4-β-PDD低11.7倍。佛波酯和远侧霉素均未刺激正常人血小板释放14C-花生四烯酸，且两者都能使阿司匹林处理过的血小板聚集。这些结果表明，佛波酯和吲哚生物碱这两类结构不同的肿瘤促进剂的代表，通过绕过花生四烯酸释放和环氧化酶依赖性花生四烯酸代谢物形成的机制，是血小板聚集、纤维蛋白原结合和颗粒/溶酶体分泌的有效激活剂。
