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

El‑Far,Ali  Hafez Ali Mohammed; Munesue,Seiichi; Harashima,Ai; Sato,Akira; Shindo,Mika; Nakajima,Shingo; Inada,Mana; Tanaka,Mariko; Takeuchi,Akihiko; Tsuchiya,Hiroyuki; Yamamoto,Hiroshi; Shaheen,Hazem  M.E.; El‑Sayed,Yasser  S.; Kawano,Shuhei; Tanuma,Sei‑Ichi; Yamamoto,Yasuhiko

doi:10.3892/ol.2018.7902

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

Authors:
- Ali Hafez Ali Mohammed El‑Far
- Seiichi Munesue
- Ai Harashima
- Akira Sato
- Mika Shindo
- Shingo Nakajima
- Mana Inada
- Mariko Tanaka
- Akihiko Takeuchi
- Hiroyuki Tsuchiya
- Hiroshi Yamamoto
- Hazem M.E. Shaheen
- Yasser S. El‑Sayed
- Shuhei Kawano
- Sei‑Ichi Tanuma
- Yasuhiko Yamamoto
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Affiliations: Department of Biochemistry and Molecular Vascular Biology, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Ishikawa 920‑8640, Japan, Department of Biochemistry, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Chiba 278‑8510, Japan, Department of Orthopedic Surgery, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Ishikawa 920‑8641, Japan, Department of Pharmacology, Faculty of Veterinary Medicine, Damanhour University, Damanhour 22511, Egypt, Department of Veterinary Forensic Medicine and Toxicology, Faculty of Veterinary Medicine, Damanhour University, Damanhour 22511, Egypt
Published online on: January 29, 2018 https://doi.org/10.3892/ol.2018.7902
Pages: 4627-4634

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Abstract

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 κ‑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.

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