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 journalArticle

140 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 languageEnglish
Pages (from-to)695-704
Number of pages10
JournalChemistry and Biology
Volume10
Issue number8
DOIs
Publication statusPublished - 2003 Aug 1

Fingerprint

CD13 Antigens
Curcumin
Angiogenesis Inhibitors
Tumors
Cells
Neoplasms
Surface Plasmon Resonance
Surface plasmon resonance
Metalloproteases
Fibroblast Growth Factor 2
Biological Products
Zinc
Assays
Membranes

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmacology
  • Drug Discovery
  • Clinical Biochemistry

Cite this

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. / Irreversible inhibition of CD13/aminopeptidase N by the antiangiogenic agent curcumin. In: Chemistry and Biology. 2003 ; Vol. 10, No. 8. pp. 695-704.
@article{38413a1de1574e30ae38446b95485fa9,
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}",
year = "2003",
month = "8",
day = "1",
doi = "10.1016/S1074-5521(03)00169-8",
language = "English",
volume = "10",
pages = "695--704",
journal = "Cell Chemical Biology",
issn = "2451-9448",
publisher = "Elsevier Inc.",
number = "8",

}

Shim, JS, Kim, JH, Cho, HY, Yum, YN, Kim, SH, Park, HJ, Shim, BS, Choi, SH & Kwon, HJ 2003, 'Irreversible inhibition of CD13/aminopeptidase N by the antiangiogenic agent curcumin', Chemistry and Biology, vol. 10, no. 8, pp. 695-704. https://doi.org/10.1016/S1074-5521(03)00169-8

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 journalArticle

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 -