Cordycepin suppresses TNF‐alpha‐induced invasion, migration and matrix metalloproteinase‐9 expression in human bladder cancer cells

Cordycepin (3′‐deoxyadenosine), a nucleoside derivative isolated from Cordyceps militaris, reportedly has antitumor effects, but its effect on the regulation of matrix metalloproteinases‐9 (MMP‐9), which regulates invasion and migration by cancer cells, has not been clearly elucidated. Cancer cell invasion and migration was investigated using a Matrigel invasion assay and wound healing analysis in two different bladder cancer cell lines: 5637 and T‐24. The results of the present study show that TNF‐α‐induced invasion and migration of cancer cells were inhibited by cordycepin. In addition, cordycepin inhibited TNF‐α‐induced proliferation in cancer cells, independent of the apoptosis pathway. Furthermore, the TNF‐α‐induced MMP‐9 expression was suppressed by cordycepin, but MMP‐2 expression was not. The inhibited MMP‐9 expression by cordycepin was associated with a decreased promoter activity of the MMP‐9 gene. Finally, cordycepin reduced the transcriptional activity of the transcription factors, nuclear factor kappaB (NF‐βB) and activator protein‐1 (AP‐1), which were identified by gel‐shift assay as cis‐elements for TNF‐α activation of the MMP‐9 promoter in both bladder cancer cell lines. These results suggest that cordycepin maybe an effective therapeutic approach to treat bladder cancer. Copyright © 2010 John Wiley & Sons, Ltd.