In vitro anticancer effects of a RAGE inhibitor discovered using a structure-based drug design system

被引：28

作者：

El-Far, Ali Hafez Ali Mohammed ^{[1
,2
]}

Munesue, Seiichi ^{[1
]}

Harashima, Ai ^{[1
]}

Sato, Akira ^{[3
]}

Shindo, Mika ^{[3
]}

Nakajima, Shingo ^{[3
]}

Inada, Mana ^{[3
]}

Tanaka, Mariko ^{[1
]}

Takeuchi, Akihiko ^{[4
]}

Tsuchiya, Hiroyuki ^{[4
]}

Yamamoto, Hiroshi ^{[1
]}

Shaheen, Hazem M. E. ^{[5
]}

El-Sayed, Yasser S. ^{[6
]}

Kawano, Shuhei ^{[1
]}

Tanuma, Sei-Ichi ^{[3
]}

Yamamoto, Yasuhiko ^{[1
]}

机构：

[1] Kanazawa Univ, Grad Sch Med Sci, Dept Biochem & Mol Vasc Biol, 13-1 Takara Machi, Kanazawa, Ishikawa 9208640, Japan

[2] Damanhour Univ, Dept Biochem, Fac Vet Med, Damanhour 22511, Egypt

[3] Tokyo Univ Sci, Fac Pharmaceut Sci, Dept Biochem, Chiba 2788510, Japan

[4] Kanazawa Univ, Grad Sch Med Sci, Dept Orthoped Surg, Kanazawa, Ishikawa 9208641, Japan

[5] Damanhour Univ, Fac Vet Med, Dept Pharmacol, Damanhour 22511, Egypt

[6] Damanhour Univ, Fac Vet Med, Dept Vet Forens Med & Toxicol, Damanhour 22511, Egypt

来源：

ONCOLOGY LETTERS | 2018年 / 15卷 / 04期

基金：

日本学术振兴会;

关键词：

receptor for advanced glycation end-products; cancer malignancy; papaverine; fibrosarcoma cells; GLYCATION END-PRODUCTS; MOLECULAR-WEIGHT HEPARIN; COLON-CANCER; DIABETIC-NEPHROPATHY; CYTOPLASMIC DOMAIN; SIGNALING PATHWAYS; NEURITE OUTGROWTH; CELL-SURFACE; RECEPTOR; EXPRESSION;

D O I：

10.3892/ol.2018.7902

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Receptor for advanced glycation end-products ( RAGE) is a pattern recognition receptor implicated in the pathogenesis of certain types of cancer. In the present study, papaverine was identified as a RAGE inhibitor using the conversion to small molecules through optimized-peptide strategy drug design system. Papaverine significantly inhibited RAGE-dependent nuclear factor kappa-B activation driven by high mobility group box-1, a RAGE ligand. Using RAGE- or dominant-negative RAGE-expressing HT1080 human fibrosarcoma cells, the present study revealed that papaverine suppressed RAGE-dependent cell proliferation and migration dose-dependently. Furthermore, papaverine significantly inhibited cell invasion. The results of the present study suggested that papaverine could inhibit RAGE, and provided novel insights into the field of RAGE biology, particularly anticancer therapies.

引用

页码：4627 / 4634

页数：8

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