Centre for Biodiscovery and School of Biological Sciences, Victoria University of Wellington, Wellington, New Zealand.
Invest New Drugs. 2011 Aug;29(4):544-53. doi: 10.1007/s10637-010-9387-5. Epub 2010 Jan 27.
Peloruside A, isolated from the marine sponge Mycale hentscheli, has a similar mechanism of action to paclitaxel (Taxol®), a drug used clinically to treat tumors of the breast, ovary and lung. Paclitaxel and peloruside stabilize the polymerized form of tubulin and arrest cells in G₂/M of the cell cycle. We have therefore used two-dimensional electrophoresis of proteins to examine the effect of peloruside A on the human HL-60 promyeloid leukemic cell line. Our goals included investigation whether affected proteins could be mapped onto pathways that predicted the cellular effects of this compound. In response to 100 nM peloruside A treatment for 24 h, seventeen identified proteins showed significant change in abundance with fourteen increases and three decreases. Use of Ingenuity Pathways Analysis confirmed that peloruside A affected pathways consistent with the known effects on microtubules and apoptosis. Our results also indicate a potential role of c-Myc in the cellular actions of peloruside consistent with an induction of aneuploidy seen at low concentrations of peloruside.
从海洋海绵 Mycale hentscheli 中分离得到的 Peloruside A 与紫杉醇（Taxol®）具有相似的作用机制，紫杉醇是一种临床上用于治疗乳腺癌、卵巢癌和肺癌的药物。紫杉醇和 Peloruside A 稳定微管蛋白的聚合形式，并将细胞阻滞在细胞周期的 G₂/M 期。因此，我们使用二维电泳技术研究了 Peloruside A 对人 HL-60 早幼粒细胞白血病细胞系的影响。我们的目标包括研究受影响的蛋白质是否可以映射到预测该化合物细胞作用的途径上。在对 100 nM Peloruside A 处理 24 小时后，有 17 种鉴定出的蛋白质的丰度发生了显著变化，其中 14 种增加，3 种减少。使用 Ingenuity Pathways Analysis 证实，Peloruside A 影响的途径与已知的对微管和细胞凋亡的作用一致。我们的结果还表明，c-Myc 在 Peloruside A 的细胞作用中可能发挥作用，这与在低浓度 Peloruside 下观察到的非整倍体的诱导一致。
