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-KB) 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.
Lee
Eo-Jin
EJ
Department of Food and Biotechnology, Chungju National University, Chungju, Chungbuk 380-702, South Korea.
Kim
Wun-Jae
WJ
Moon
Sung-Kwon
SK
D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D003839:Deoxyadenosines / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D001749:Urinary Bladder Neoplasms / Q000235:genetics / Q000378:metabolism*
D000970:Antineoplastic Agents; D003839:Deoxyadenosines; D016328:NF-kappa B; D018808:Transcription Factor AP-1; D014409:Tumor Necrosis Factor-alpha; D020780:Matrix Metalloproteinase 9; C058120:cordycepin