Valproic acid counteracts polycyclic aromatic hydrocarbons (PAHs)-induced tumorigenic effects by regulating the polarization of macrophages
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 nor...
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| Format: | Article |
| Language: | English |
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Elsevier
2022-08-01
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| Series: | Ecotoxicology and Environmental Safety |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0147651322006194 |
| _version_ | 1811291998715379712 |
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| author | Yisha Zhang David Lim Zuchao Cai Junxuan Peng Beidi Jia Guoliang Chu Fengmei Zhang Chao Dong Zhihui Feng |
| author_facet | Yisha Zhang David Lim Zuchao Cai Junxuan Peng Beidi Jia Guoliang Chu Fengmei Zhang Chao Dong Zhihui Feng |
| author_sort | Yisha Zhang |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-13T04:38:52Z |
| format | Article |
| id | doaj.art-74a2c93b1b9b4e018bcbf6697201ee9b |
| institution | Directory Open Access Journal |
| issn | 0147-6513 |
| language | English |
| last_indexed | 2024-04-13T04:38:52Z |
| publishDate | 2022-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Ecotoxicology and Environmental Safety |
| spelling | doaj.art-74a2c93b1b9b4e018bcbf6697201ee9b2022-12-22T03:02:05ZengElsevierEcotoxicology and Environmental Safety0147-65132022-08-01241113779Valproic acid counteracts polycyclic aromatic hydrocarbons (PAHs)-induced tumorigenic effects by regulating the polarization of macrophagesYisha Zhang0David Lim1Zuchao Cai2Junxuan Peng3Beidi Jia4Guoliang Chu5Fengmei Zhang6Chao Dong7Zhihui Feng8Department of Occupational Health and Occupational Medicine, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan 250012, Shandong, ChinaTranslational Health Research Institute, School of Health Sciences, Western Sydney University, Campbelltown, New South Wales, Australia; College of Medicine and Public Health, Flinders University, Bedford Park, South Australia, AustraliaDepartment of Occupational Health and Occupational Medicine, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan 250012, Shandong, ChinaDepartment of Occupational Health and Occupational Medicine, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan 250012, Shandong, ChinaDepartment of Occupational Health and Occupational Medicine, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan 250012, Shandong, ChinaDepartment of Occupational Health and Occupational Medicine, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan 250012, Shandong, ChinaDepartment of Occupational Health and Occupational Medicine, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan 250012, Shandong, ChinaDepartment of Occupational Health and Occupational Medicine, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan 250012, Shandong, China; Correspondence to: Department of Occupational Health and Occupational Medicine, School of Public Health, Cheeloo College of Medicine, Shandong University, 44 Wenhua Xi Road, Jinan 250012, Shandong, China.Department of Occupational Health and Occupational Medicine, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan 250012, Shandong, China; Correspondence to: Department of Occupational Health and Occupational Medicine, School of Public Health, Cheeloo College of Medicine, Shandong University, 44 Wenhua Xi Road, Jinan 250012, Shandong, China.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.http://www.sciencedirect.com/science/article/pii/S0147651322006194PAHsVPAMacrophagesVasculature |
| spellingShingle | Yisha Zhang David Lim Zuchao Cai Junxuan Peng Beidi Jia Guoliang Chu Fengmei Zhang Chao Dong Zhihui Feng Valproic acid counteracts polycyclic aromatic hydrocarbons (PAHs)-induced tumorigenic effects by regulating the polarization of macrophages Ecotoxicology and Environmental Safety PAHs VPA Macrophages Vasculature |
| title | Valproic acid counteracts polycyclic aromatic hydrocarbons (PAHs)-induced tumorigenic effects by regulating the polarization of macrophages |
| title_full | Valproic acid counteracts polycyclic aromatic hydrocarbons (PAHs)-induced tumorigenic effects by regulating the polarization of macrophages |
| title_fullStr | Valproic acid counteracts polycyclic aromatic hydrocarbons (PAHs)-induced tumorigenic effects by regulating the polarization of macrophages |
| title_full_unstemmed | Valproic acid counteracts polycyclic aromatic hydrocarbons (PAHs)-induced tumorigenic effects by regulating the polarization of macrophages |
| title_short | Valproic acid counteracts polycyclic aromatic hydrocarbons (PAHs)-induced tumorigenic effects by regulating the polarization of macrophages |
| title_sort | valproic acid counteracts polycyclic aromatic hydrocarbons pahs induced tumorigenic effects by regulating the polarization of macrophages |
| topic | PAHs VPA Macrophages Vasculature |
| url | http://www.sciencedirect.com/science/article/pii/S0147651322006194 |
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