Proteomic profiling of oleamide-mediated polarization in a primary human monocyte-derived tumor-associated macrophages (TAMs) model: a functional analysis

Prapakorn Wisitpongpun, Cellular and Molecular Immunology Research Unit (CMIRU), Faculty of Allied Health Sciences, Naresuan University, Mueang, Phitsanulok, Thailand.
Watunyoo Buakaew, Cellular and Molecular Immunology Research Unit (CMIRU), Faculty of Allied Health Sciences, Naresuan University, Mueang, Phitsanulok, Thailand.
Sutatip Pongcharoen, Division of Immunology, Department of Medicine, Faculty of Medicine, Naresuan University, Mueang, Phitsanulok, Thailand.
Napaporn Apiratmateekul, Reference Material and Medical Laboratory Innovation Research Unit, Faculty of Allied Health Sciences, Naresuan University, Mueang, Phitsanulok, Thailand.
Pachuen Potup, Cellular and Molecular Immunology Research Unit (CMIRU), Faculty of Allied Health Sciences, Naresuan University, Mueang, Phitsanulok, Thailand.
Krai Daowtak, Cellular and Molecular Immunology Research Unit (CMIRU), Faculty of Allied Health Sciences, Naresuan University, Mueang, Phitsanulok, Thailand.
Sucheewin Krobthong, Center of Excellence in Natural Products Chemistry (CENP), Department of Chemistry Faculty of Science, Chulalongkorn University, Bangkok, Thailand.
Yodying Yingchutrakul, National Center for Genetic Engineering and Biotechnology, NSTDA, Pathum Thani, Thailand.
Paul J. Brindley, Department of Microbiology, Immunology and Tropical Medicine, and Research Center for Neglected Diseases of Poverty, School of Medicine & Health Sciences, George Washington University, District of Columbia, WA, United States of America.
Kanchana Usuwanthim, Cellular and Molecular Immunology Research Unit (CMIRU), Faculty of Allied Health Sciences, Naresuan University, Mueang, Phitsanulok, Thailand.

Document Type

Journal Article

Publication Date

1-1-2024

Journal

PeerJ

Volume

12

DOI

10.7717/peerj.18090

Keywords

Molecular docking; Oleamide; Proteomic; Tumor-associated macrophages

Abstract

BACKGROUND: Tumor-associated macrophages (TAMs) play a critical function in the development of tumors and are associated with protumor M2 phenotypes. Shifting TAMs towards antitumor M1 phenotypes holds promise for tumor immunotherapy. Oleamide, a primary fatty acid amide, has emerged as a potent anticancer and immunomodulatory compound. However, the regulatory effects of oleamide on TAM phenotypes remain unclear. METHODS: We used real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA) techniques to study the influence of oleamide on primary human monocyte-derived TAM phenotypes, and we investigated the protein expression profiles based on mass spectrometry to analyze the effect of oleamide on macrophage polarization. Moreover, the advantageous binding scores between oleamide and these target candidate proteins are examined using molecular docking. RESULTS: Our study revealed that oleamide effectively suppressed the M2-like TAM phenotype by reducing interleukin (IL)-10 production and downregulating M2-like markers, including vascular endothelial growth factor A (VEGFA), MYC proto-oncogene, bHLH transcription factor (c-Myc), and mannose receptor C-type 1 (CD206). Moreover, the conditioned medium derived from oleamide-treated TAMs induces apoptosis of MDA-MB-231 breast cancer cells. Proteomic analysis identified 20 candidate up- and down-regulation proteins targeted by oleamide, showing modulation activity associated with the promotion of the M1-like phenotype. Furthermore, molecular docking demonstrated favorable binding scores between oleamide and these candidate proteins. Collectively, our findings suggest that oleamide exerts a potent antitumor effect by promoting the antitumor M1-like TAM phenotype. These novel insights provide valuable resources for further investigations into oleamide and macrophage polarization which inhibit the progression of breast cancer, which may provide insight into immunotherapeutic approaches for cancer.

Department

Microbiology, Immunology, and Tropical Medicine

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