Irreversible inhibition of CD13/aminopeptidase N by the antiangiogenic agent curcumin

Joong Sup Shim; Jin Hee Kim; Hyun Young Cho; Young Na Yum; Seung Hee Kim; Hyun Ju Park; Bum Sang Shim; Seung Hoon Choi; Ho Jeong Kwon

doi:10.1016/S1074-5521(03)00169-8

Irreversible inhibition of CD13/aminopeptidase N by the antiangiogenic agent curcumin

Joong Sup Shim, Jin Hee Kim, Hyun Young Cho, Young Na Yum, Seung Hee Kim, Hyun Ju Park, Bum Sang Shim, Seung Hoon Choi, Ho Jeong Kwon

Research output: Contribution to journal › Article › peer-review

172 Citations (Scopus)

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	https://doi.org/10.1016/S1074-5521(03)00169-8
Publication status	Published - 2003 Aug 1

Bibliographical note

Funding 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

Biochemistry
Molecular Medicine
Molecular Biology
Pharmacology
Drug Discovery
Clinical Biochemistry

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title = "Irreversible inhibition of CD13/aminopeptidase N by the antiangiogenic agent curcumin",

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.",

author = "Shim, {Joong Sup} and Kim, {Jin Hee} and Cho, {Hyun Young} and Yum, {Young Na} and Kim, {Seung Hee} and Park, {Hyun Ju} and Shim, {Bum Sang} and Choi, {Seung Hoon} and Kwon, {Ho Jeong}",

note = "Funding 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.",

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doi = "10.1016/S1074-5521(03)00169-8",

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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

N1 - Funding 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.

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.

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Irreversible inhibition of CD13/aminopeptidase N by the antiangiogenic agent curcumin

Abstract

Bibliographical note

All Science Journal Classification (ASJC) codes

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