Valproic acid counteracts polycyclic aromatic hydrocarbons (PAHs)-induced tumorigenic effects by regulating the polarization of macrophages.

Zhang, Y; Lim, D; Cai, Z; Peng, J; Jia, B; Chu, G; Zhang, F; Dong, C; Feng, Z

Valproic acid counteracts polycyclic aromatic hydrocarbons (PAHs)-induced tumorigenic effects by regulating the polarization of macrophages.

Zhang, Y Lim, D Cai, Z Peng, J Jia, B Chu, G Zhang, F Dong, C Feng, Z

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Publisher:: Elsevier
Publication Type:: Journal Article
Citation:: Ecotoxicol Environ Saf, 2022, 241, pp. 113779
Issue Date:: 2022-08

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Field	Value	Language
dc.contributor.author	Zhang, Y
dc.contributor.author	Lim, D
dc.contributor.author	Cai, Z
dc.contributor.author	Peng, J
dc.contributor.author	Jia, B
dc.contributor.author	Chu, G
dc.contributor.author	Zhang, F
dc.contributor.author	Dong, C
dc.contributor.author	Feng, Z
dc.date.accessioned	2023-07-17T05:16:11Z
dc.date.available	2022-06-14
dc.date.available	2023-07-17T05:16:11Z
dc.date.issued	2022-08
dc.identifier.citation	Ecotoxicol Environ Saf, 2022, 241, pp. 113779
dc.identifier.issn	0147-6513
dc.identifier.issn	1090-2414
dc.identifier.uri	http://hdl.handle.net/10453/171558
dc.description.abstract	Polycyclic aromatic hydrocarbons (PAHs) are common persistent organic pollutants that are carcinogenic, teratogenic and mutagenic, causing a variety of harm to human health. In this study, we investigated the mechanism of how valproic acid (VPA) interferes with the carcinogenesis of PAHs protect normal tissues via the regulation of macrophages' function. Using the established model of transformed malignant breast cancer by 7,12-dimethylbenz[a]anthracene (DMBA), a representative PAH carcinogen, we discovered VPA induces the polarization of macrophages toward the M1 phenotype in the tumor tissues, facilitates the expression of pro-inflammatory cytokines such as IFN-γ, IL-12 and TNF-α, activates CD8+ T cells to secret Granzyme B thus to promote the apoptosis of tumor cells and suppresses the viability of vascular endothelial cells in tissue stroma of tumor. Surprisingly, VPA selectively induces macrophages to polarize towards the M2 phenotype in normal tissues and promotes the expression of anti-inflammatory cytokines such as IL-10 to enhance cell proliferation. Additionally, at the cellular level, VPA can directly regulate the polarization of macrophages to affect the growth of vascular endothelial cells by simulating the living conditions of tumor and normal cells. Collectively, VPA exerts an interventional effect on tumor growth and a protective effect on normal tissues by regulation of selective macrophages' polarization in their microenvironment.
dc.format	Print-Electronic
dc.language	eng
dc.publisher	Elsevier
dc.relation.ispartof	Ecotoxicol Environ Saf
dc.relation.isbasedon	10.1016/j.ecoenv.2022.113779
dc.rights	info:eu-repo/semantics/openAccess
dc.subject	03 Chemical Sciences, 05 Environmental Sciences, 11 Medical and Health Sciences
dc.subject.classification	Strategic, Defence & Security Studies
dc.subject.classification	4011 Environmental engineering
dc.subject.classification	4102 Ecological applications
dc.subject.classification	4202 Epidemiology
dc.subject.mesh	CD8-Positive T-Lymphocytes
dc.subject.mesh	Carcinogenesis
dc.subject.mesh	Carcinogens
dc.subject.mesh	Cytokines
dc.subject.mesh	Endothelial Cells
dc.subject.mesh	Humans
dc.subject.mesh	Macrophages
dc.subject.mesh	Neoplasms
dc.subject.mesh	Polycyclic Aromatic Hydrocarbons
dc.subject.mesh	Tumor Microenvironment
dc.subject.mesh	Valproic Acid
dc.subject.mesh	CD8-Positive T-Lymphocytes
dc.subject.mesh	Macrophages
dc.subject.mesh	Endothelial Cells
dc.subject.mesh	Humans
dc.subject.mesh	Neoplasms
dc.subject.mesh	Valproic Acid
dc.subject.mesh	Cytokines
dc.subject.mesh	Carcinogens
dc.subject.mesh	Tumor Microenvironment
dc.subject.mesh	Carcinogenesis
dc.subject.mesh	Polycyclic Aromatic Hydrocarbons
dc.subject.mesh	CD8-Positive T-Lymphocytes
dc.subject.mesh	Carcinogenesis
dc.subject.mesh	Carcinogens
dc.subject.mesh	Cytokines
dc.subject.mesh	Endothelial Cells
dc.subject.mesh	Humans
dc.subject.mesh	Macrophages
dc.subject.mesh	Neoplasms
dc.subject.mesh	Polycyclic Aromatic Hydrocarbons
dc.subject.mesh	Tumor Microenvironment
dc.subject.mesh	Valproic Acid
dc.title	Valproic acid counteracts polycyclic aromatic hydrocarbons (PAHs)-induced tumorigenic effects by regulating the polarization of macrophages.
dc.type	Journal Article
utslib.citation.volume	241
utslib.location.activity	Netherlands
utslib.for	03 Chemical Sciences
utslib.for	05 Environmental Sciences
utslib.for	11 Medical and Health Sciences
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Health
pubs.organisational-group	/University of Technology Sydney/Faculty of Health/IMPACCT
utslib.copyright.status	open_access	*
dc.date.updated	2023-07-17T05:16:09Z
pubs.publication-status	Published
pubs.volume	241

Abstract:

Polycyclic aromatic hydrocarbons (PAHs) are common persistent organic pollutants that are carcinogenic, teratogenic and mutagenic, causing a variety of harm to human health. In this study, we investigated the mechanism of how valproic acid (VPA) interferes with the carcinogenesis of PAHs protect normal tissues via the regulation of macrophages' function. Using the established model of transformed malignant breast cancer by 7,12-dimethylbenz[a]anthracene (DMBA), a representative PAH carcinogen, we discovered VPA induces the polarization of macrophages toward the M1 phenotype in the tumor tissues, facilitates the expression of pro-inflammatory cytokines such as IFN-γ, IL-12 and TNF-α, activates CD8+ T cells to secret Granzyme B thus to promote the apoptosis of tumor cells and suppresses the viability of vascular endothelial cells in tissue stroma of tumor. Surprisingly, VPA selectively induces macrophages to polarize towards the M2 phenotype in normal tissues and promotes the expression of anti-inflammatory cytokines such as IL-10 to enhance cell proliferation. Additionally, at the cellular level, VPA can directly regulate the polarization of macrophages to affect the growth of vascular endothelial cells by simulating the living conditions of tumor and normal cells. Collectively, VPA exerts an interventional effect on tumor growth and a protective effect on normal tissues by regulation of selective macrophages' polarization in their microenvironment.

Please use this identifier to cite or link to this item:

http://hdl.handle.net/10453/171558