Benzina Sami, Harquail Jason, Jean Stephanie, Beauregard Annie-Pier, Colquhoun Caitlyn D, Carroll Madison, Bos Allyson, Gray Christopher A, Robichaud Gilles A
Universite de Moncton, Moncton, NB, Canada, E1A3E9.
Anticancer Agents Med Chem. 2015;15(1):79-88. doi: 10.2174/1871520614666140608150448.
The study of anticancer properties from natural products has regained popularity as natural molecules provide a high diversity of chemical structures with specific biological and medicinal activity. Based on a documented library of the most common medicinal plants used by the indigenous people of North America, we screened and isolated compounds with anti-breast cancer properties from Juniperus communis (common Juniper). Using bioassay-guided fractionation of a crude plant extract, we identified the diterpene isocupressic acid and the aryltetralin lignan deoxypodophyllotoxin (DPT) as potent inducers of caspase-dependent programmed cell death (apoptosis) in malignant MB231 breast cancer cells. Further elucidation revealed that DPT, in contrast to isocupressic acid, also concomitantly inhibited cell survival pathways mediated by the MAPK/ERK and NFκB signaling pathways within hours of treatment. Our findings emphasize the potential and importance of natural product screening for new chemical entities with novel anticancer activities. Natural products research complemented with the wealth of information available through the ethnobotanical and ethnopharmacological knowledge of the indigenous peoples of North America can provide new candidate entities with desirable bioactivities to develop new cancer therapies.
由于天然分子具有具有特定生物和药用活性的高度多样化化学结构，对天然产物抗癌特性的研究再度受到关注。基于北美原住民使用的最常见药用植物的文献库，我们从杜松（普通杜松）中筛选并分离出具有抗乳腺癌特性的化合物。通过对粗植物提取物进行生物测定指导的分级分离，我们确定二萜类异柏酸和芳基四氢萘木脂素脱氧鬼臼毒素（DPT）是恶性MB231乳腺癌细胞中半胱天冬酶依赖性程序性细胞死亡（凋亡）的有效诱导剂。进一步的研究表明，与异柏酸不同，DPT在处理后数小时内还同时抑制了由MAPK/ERK和NFκB信号通路介导的细胞存活途径。我们的研究结果强调了天然产物筛选对于具有新型抗癌活性的新化学实体的潜力和重要性。天然产物研究与通过北美原住民的民族植物学和民族药理学知识获得的丰富信息相结合，可以提供具有理想生物活性的新候选实体，以开发新的癌症治疗方法。
