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Our previous studies have clearly shown that the angiogenic enzymes, matrix metalloproteinase (MMP) ‐2/9, are directly involved in human hepatic tumorigenesis and metastasis and suggest that the MMP‐2/9 inhibitors, which have dual inhibitory activi¬ties on enzyme activity and transcription, represent the best candidates for achieving tumor regression. Many anti‐cancer drugs have strong cellular cytotoxicity and side effects, indicating that strong anti‐cancer drugs that have no or minimal cytotoxicity and side effects need to be developed. The specific aim of the present study was to develop powerful anti‐cancer drugs with specific tumor regression and anti‐metastatic potential having the dual inhibitory activities of specific MMP‐2 and ‐9 enzyme activities and gene transcription at the molecular level. Caffeic acid (CA), a strong and selective MMP‐9 activity and transcription inhibitor, was isolated from the plant …