Coix seed extract, a commonly used treatment for cancer in China, inhibits NFkappaB and protein kinase C signaling.
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.
Woo
Ju-Hyung
JH
The Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Li
Dapeng
D
Wilsbach
Kathleen
K
Orita
Hajime
H
Coulter
Jonathan
J
Tully
Ellen
E
Kwon
Taeg Kyu
TK
Xu
Shi
S
Gabrielson
Edward
E
D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology* / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor / Q000187:drug effects / Q000637:transplantation; D031742:Coix / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000494:pharmacology* / Q000627:therapeutic use; D004655:Emulsions; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008517:Phytotherapy; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D012639:Seeds / Q000737:chemistry; D015398:Signal Transduction / Q000187:drug effects*; D051996:Transcription Factor RelA / Q000037:antagonists & inhibitors* / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
D000972:Antineoplastic Agents, Phytogenic; D004365:Drugs, Chinese Herbal; D004655:Emulsions; D009363:Neoplasm Proteins; D051996:Transcription Factor RelA; D011493:Protein Kinase C