Inhibition of tumor growth by a newly-identified activator for epidermal fatty acid binding protein
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Enyu Rao1, Puja Singh1, Xiuhong Zhai1, Yan Li1, Ganqian Zhu1, Yuwen Zhang1, Jiaqing Hao1, Young-In Chi1, Rhoderick E. Brown1, Margot P. Cleary1 and Bing Li1
1 The Hormel Institute, University of Minnesota, Austin, MN, USA
Bing Li, email:
Keywords: E-FABP, tumor associated macrophages, interferon β, tumor treatment
Received: November 20, 2015 Accepted: February 04, 2015 Published: March 08, 2015
Our previous studies have demonstrated that expression of epidermal fatty acid binding protein (E-FABP) in tumor associated macrophages (TAMs) promotes macrophage anti-tumor activity by enhancing IFNβ responses in tumor models. Thus, E-FABP represents a new protective factor in enhancing tumor immune surveillance against tumor development. Herein, we report the compound 5-(benzylamino)-2-(3-methylphenyl)-1,3-oxazole-4-carbonitrile (designated EI-05) as a novel E-FABP activator for inhibition of mammary tumor growth. EI-05 was selected from the ZINC compound library using molecular docking analysis based on the crystal structure of E-FABP. Although EI-05 is unable to bind E-FABP directly, it significantly increases E-FABP expression in macrophages during inflammation. Stimulation of macrophages with EI-05 remarkably enhances lipid droplet formation and IFNβ production, which further promotes the anti-tumor activity of macrophages. Importantly, administering EI-05 in vivo significantly inhibits mammary tumor growth in a syngeneic mouse model. Altogether, these results suggest that EI-05 may represent a promising drug candidate for anti-tumor treatment through enhancing E-FABP activity and IFNβ responses in macrophages.
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