Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 695-704 |
| Number of pages | 10 |
| Journal | Chemistry and Biology |
| Volume | 10 |
| Issue number | 8 |
| DOIs | |
| Publication status | Published - 2003 Aug 1 |
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All Science Journal Classification (ASJC) codes
- Biochemistry
- Molecular Medicine
- Molecular Biology
- Pharmacology
- Drug Discovery
- Clinical Biochemistry
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Irreversible inhibition of CD13/aminopeptidase N by the antiangiogenic agent curcumin. / Shim, Joong Sup; Kim, Jin Hee; Cho, Hyun Young; Yum, Young Na; Kim, Seung Hee; Park, Hyun Ju; Shim, Bum Sang; Choi, Seung Hoon; Kwon, Ho Jeong.
In: Chemistry and Biology, Vol. 10, No. 8, 01.08.2003, p. 695-704.Research output: Contribution to journal › Article
TY - JOUR
T1 - Irreversible inhibition of CD13/aminopeptidase N by the antiangiogenic agent curcumin
AU - Shim, Joong Sup
AU - Kim, Jin Hee
AU - Cho, Hyun Young
AU - Yum, Young Na
AU - Kim, Seung Hee
AU - Park, Hyun Ju
AU - Shim, Bum Sang
AU - Choi, Seung Hoon
AU - Kwon, Ho Jeong
PY - 2003/8/1
Y1 - 2003/8/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0041914004&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0041914004&partnerID=8YFLogxK
U2 - 10.1016/S1074-5521(03)00169-8
DO - 10.1016/S1074-5521(03)00169-8
M3 - Article
C2 - 12954328
AN - SCOPUS:0041914004
VL - 10
SP - 695
EP - 704
JO - Cell Chemical Biology
JF - Cell Chemical Biology
SN - 2451-9448
IS - 8
ER -