Coix seed extract, a commonly used treatment for cancer in china, inhibits NFκB and protein kinase C signaling
Coix seed extract, a commonly used treatment for cancer in china, inhibits NFκB and protein kinase C signaling
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DOI：
10.4161/cbt.6.12.5168
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发表时间：
2007-12-01
影响因子：
3.6
通讯作者：
Gabrielson, Edward
中科院分区：
文献类型：
--
作者：
Woo, Ju- Hyung;Li, Dapeng;Gabrielson, Edward
药用级薏苡仁提取物是目前中国最常用的癌症治疗方法。尽管临床数据支持该中药制剂用于癌症治疗，但该制剂活性的生物学基础此前尚未确定。为了解决这个问题，我们首先评估了薏苡仁提取物乳剂在MDA-MB-231乳腺癌细胞异种移植物中的抗肿瘤活性，发现该提取物显着抑制无胸腺裸鼠中MDA-MB-231异种移植物的生长。使用寡核苷酸微阵列，我们确定薏苡仁提取物还显着影响这些细胞中的基因表达，包括下调被认为在肿瘤形成中重要的基因（例如COX-2和基质金属蛋白酶）。薏苡仁提取物处理后注意到的特定基因表达变化是 NF kappa B 依赖性转录抑制的特征，使我们能够评估处理如何影响该途径。 NF kappa B 依赖性报告分析表明，用提取物处理培养物可剂量依赖性抑制 NF kappa B 信号传导，免疫荧光显微镜发现这些效应与 NF kappa B 的 Rel-A/p65 亚基向细胞核易位减少有关。薏苡仁提取物还可以抑制蛋白激酶 C 的活性，蛋白激酶 C 是信号转导的主要介质和 NF kappa B 的激活剂。因此，这种基于传统中医的癌症治疗方法会影响肿瘤形成中公认的重要细胞通路。
A pharmaceutical grade extract of Coix lachryma-jobi seeds is currently the most commonly used treatment for cancer in China. Although clinical data support the use of this preparation of a Traditional Chinese Medicine for cancer treatment, biological basis for the activity of this preparation has not been previously established. To address this issue, we first evaluated the anti-neoplastic activity of a Coix extract emulsion in xenografts of MDA-MB-231 breast cancer cells and found that the extract significantly inhibits growth of MDA-MB-231 xenografts in athymic nude mice. Using oligonucleotide microarrays, we determined that Coix seed extract also significantly affects gene expression in these cells, including downregulation of genes (such as COX-2 and matrixmetalloproteinases) that are considered to be important in neoplasia. The specific gene expression changes noted after Coix seed extract treatment are characteristic of inhibition of NF kappa B-dependent transcription, leading us to evaluate how the treatment affects that pathway. An NF kappa B-dependent reporter assay demonstrated dose-dependant inhibition of NF kappa B signaling by treatment of cultures with the extract, and immunofluorescent microscopy found that these effects are associated with reduced translocation of the Rel-A/p65 subunit of NF kappa B to the nucleus. Coix extract also inhibits activity of protein kinase C, a major mediator of signal transcluction and activator of NF kappa B. Thus, this Traditional Chinese Medicine-based cancer treatment affects cellular pathways of recognized importance in neoplasia.