Inhibition of tumor growth by a newly-identified activator for epidermal fatty acid binding protein

// Enyu Rao 1 , Puja Singh 1 , Xiuhong Zhai 1 , Yan Li 1 , Ganqian Zhu 1 , Yuwen Zhang 1 , Jiaqing Hao 1 , Young-In Chi 1 , Rhoderick E. Brown 1 , Margot P. Cleary 1 and Bing Li 1 1 The Hormel Institute, University of Minnesota, Austin, MN, USA Correspondence to: 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 Abstract 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.