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

doi:10.18632/oncotarget.3485

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

Journal article

Open access

Peer reviewed

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, …

Oncotarget, Vol.6(10), pp.7815-7827

04/10/2015

DOI: 10.18632/oncotarget.3485

PMCID: PMC4480718

PMID: 25796556

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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.

Animals

Fatty Acid-Binding Proteins - biosynthesis

Fatty Acid-Binding Proteins - metabolism

Female

Humans

Interferon-beta - biosynthesis

Interferon-beta - metabolism

Macrophage Activation - drug effects

Macrophages - drug effects

Macrophages - metabolism

Mammary Neoplasms, Experimental - drug therapy

Mammary Neoplasms, Experimental - metabolism

Mice

Models, Molecular

Nitriles - chemistry

Nitriles - pharmacology

Oxazoles - chemistry

Oxazoles - pharmacology

Details

Title: Subtitle: Inhibition of tumor growth by a newly-identified activator for epidermal fatty acid binding protein
Creators: Enyu Rao - Hormel (United States)
Puja Singh - Hormel (United States)
Xiuhong Zhai - Hormel (United States)
Yan Li - Hormel (United States)
Ganqian Zhu - Hormel (United States)
Yuwen Zhang - University of Minnesota
Jiaqing Hao - Hormel (United States)
Young-In Chi - Hormel (United States)
Rhoderick E Brown - Hormel (United States)
Margot P Cleary - University of Minnesota
Bing Li - Hormel (United States)
Resource Type: Journal article
Publication Details: Oncotarget, Vol.6(10), pp.7815-7827
DOI: 10.18632/oncotarget.3485
PMID: 25796556
PMCID: PMC4480718
NLM abbreviation: Oncotarget
ISSN: 1949-2553
eISSN: 1949-2553
Publisher: Impact Journals LLC
Grant note: R01 CA157012 / NCI NIH HHS R01 HL125353 / NHLBI NIH HHS R01 CA180986 / NCI NIH HHS R01 CA177679 / NCI NIH HHS R01 GM45928 / NIGMS NIH HHS R01 GM045928 / NIGMS NIH HHS
Language: English
Date published: 04/10/2015
Academic Unit: Pathology; Surgery
Record Identifier: 9984695802602771

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