Coix Seed Extract, a Commonly Used Treatment for Cancer in China, Inhibits NFκB and Protein Kinase C Signaling

Abstract

A pharmaceutical grade extract of Coix lachryma-jobi seeds is currently the most commonly used treatment for cancer in China. Although clinical data supports 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 extract also significantly affects gene expression in these cells, including down-regulation of genes (such as COX-2 and matrixmetalloproteinases) that are considered to be important in neoplasia. The specific gene expression changes noted after Coix treatment are characteristic of inhibition of NFκB-dependant transcription, leading us to evaluate how the treatment affects that pathway. An NFκB-dependant reporter assay demonstrated dose-dependant inhibition of NFκB 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 NFκB to the nucleus. Coix extract also inhibits activity of protein kinase C, a major mediator of signal transduction and activator of NFκB. Thus, this Traditional Chinese Medicine-based cancer treatment affects cellular pathways of recognized importance in neoplasia. Key words : Coix extract, Traditional Chinese Medicine, NFκB, COX-2