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

Oncol Lett. 2018 Apr;15(4):4627-4634. doi: 10.3892/ol.2018.7902. Epub 2018 Jan 29.


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.

Keywords: cancer malignancy; fibrosarcoma cells; papaverine; receptor for advanced glycation end-products.