CD13/aminopeptidase N (APN) is a membrane-bound, zinc-dependent metalloproteinase that plays a key role in tumor invasion and angiogenesis. Here, we show that curcumin, a phenolic natural product, binds to APN and irreversibly inhibits its activity. The direct interaction between curcumin with APN was confirmed both in vitro and in vivo by surface plasmon resonance analysis and an APN-specific antibody competition assay, respectively. Moreover, curcumin and other known APN inhibitors strongly inhibited APN-positive tumor cell invasion and basic fibroblast growth factor-induced angiogenesis. However, curcumin did not inhibit the invasion of APN-negative tumor cells, suggesting that the antiinvasive activity of curcumin against tumor cells is attributable to the inhibition of APN. Taken together, our study revealed that curcumin is a novel irreversible inhibitor of APN that binds to curcumin resulting in inhibition of angiogenesis.
Bibliographical noteFunding Information:
We are grateful to Drs. H. Kleinman, J.D. Dawson, and T.K. Kim for their critical reading of the manuscript. This study was supported by a grant from the Ministry of Health & Welfare, Republic of Korea (HMP-99-D-01-0004) and the Brain Korea 21 Project.
All Science Journal Classification (ASJC) codes
- Molecular Medicine
- Molecular Biology
- Drug Discovery
- Clinical Biochemistry