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

Enyu Rao, Puja Singh, Xiuhong Zhai, Yan Li, Ganqian Zhu, Yuwen Zhang, Jiaqing Hao, Young-In Chi, Rhoderick E Brown, Margot P Cleary, Bing Li

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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.

Original languageEnglish (US)
Pages (from-to)7815-7827
Number of pages13
JournalOncotarget
Volume6
Issue number10
DOIs
StatePublished - Jan 1 2015

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Keywords

  • E-FABP
  • Interferon β
  • Tumor associated macrophages
  • Tumor treatment

Cite this

Rao, E., Singh, P., Zhai, X., Li, Y., Zhu, G., Zhang, Y., Hao, J., Chi, Y-I., Brown, R. E., Cleary, M. P., & Li, B. (2015). Inhibition of tumor growth by a newly-identified activator for epidermal fatty acid binding protein. Oncotarget, 6(10), 7815-7827. https://doi.org/10.18632/oncotarget.3485