A novel plant toxin, persin, with in vivo activity in the mammary gland, induces Bim-dependent apoptosis in human breast cancer cells
A novel plant toxin, persin, with in vivo activity in the mammary gland, induces Bim-dependent apoptosis in human breast cancer cells
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DOI：
10.1158/1535-7163.mct-06-0170
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发表时间：
2006-09-01
影响因子：
5.7
通讯作者：
Sutherland, Robert L.
中科院分区：
文献类型：
--
作者：
Butt, Alison J.;Roberts, Caroline G.;Sutherland, Robert L.
植物化学物质为癌症的治疗提供了丰富而有效的药物来源。在这里，我们描述了一种新的植物毒素的特征，persin，在乳腺中具有体内活性，并具有p53-，雌激素受体-和bcl -2独立的作用模式。先前从鳄梨叶中发现的Persin是导致哺乳期牲畜乳腺特异性坏死和细胞凋亡的毒性原理。本研究用泌乳小鼠模型证实persin对泌乳乳腺上皮具有类似的细胞毒性。在一组人乳腺癌细胞系的进一步体外研究表明，persin选择性地诱导敏感细胞的G(2)-M细胞周期阻滞和caspase依赖性凋亡。后者依赖于bh3蛋白Bim的表达。Bim是一种细胞骨架完整性的传感器，有证据表明，这种化合物的独特结构，persin可以代表一种新型的微管靶向药物，具有潜在的乳腺癌特异性。
Phytochemicals have provided an abundant and effective source of therapeutics for the treatment of cancer. Here we describe the characterization of a novel plant toxin, persin, with in vivo activity in the mammary gland and a p53-, estrogen receptor-, and Bcl-2-independent mode of action. Persin was previously identified from avocado leaves as the toxic principle responsible for mammary gland-specific necrosis and apoptosis in lactating livestock. Here we used a lactating mouse model to confirm that persin has a similar cytotoxicity for the lactating mammary epithelium. Further in vitro studies in a panel of human breast cancer cell lines show that persin selectively induces a G(2)-M cell cycle arrest and caspase-dependent apoptosis in sensitive cells. The latter is dependent on expression of the BH3-only protein Bim. Bim is a sensor of cytoskeletal integrity, and there is evidence that unique structure of the compound, persin could represent a novel class of microtubule-targeting agent with potential specificity for breast cancers.