Coix seed extract, a commonly used treatment for cancer in China, inhibits NFkappaB 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 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 NFkappaB-dependent transcription, leading us to evaluate how the treatment affects that pathway. An NFkappaB-dependent reporter assay demonstrated dose-dependant inhibition of NFkappaB 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 NFkappaB to the nucleus. Coix extract also inhibits activity of protein kinase C, a major mediator of signal transduction and activator of NFkappaB. Thus, this Traditional Chinese Medicine-based cancer treatment affects cellular pathways of recognized importance in neoplasia.