The intervention of valproic acid on the tumorigenesis induced by an environmental carcinogen of PAHs

Junxuan Peng; Zuchao Cai; Ruixue Zhao; Jiahao Chen; Guochao Liu; Chao Dong; David Lim; Zhihui Feng

doi:10.1093/toxres/tfaa069

The intervention of valproic acid on the tumorigenesis induced by an environmental carcinogen of PAHs

Toxicol Res (Camb). 2020 Aug 31;9(5):609-621. doi: 10.1093/toxres/tfaa069. eCollection 2020 Sep.

Authors

Junxuan Peng¹, Zuchao Cai¹, Ruixue Zhao¹, Jiahao Chen¹, Guochao Liu¹, Chao Dong¹, David Lim², Zhihui Feng¹

Affiliations

¹ Department of Occupational Health and Occupational Medicine, School of Public Health, Cheeloo College of Medicine, Shandong University, 44 Wenhua Xi Road, Shandong, Jinan, 250012, China.
² School of Science and Health, Western Sydney University, Narellan Road, Campbelltown NSW 2560, Australia.

Abstract

This study investigated whether valproic acid (VPA, a histone deacetylase inhibitor) can interfere with the carcinogenicity of polycyclic aromatic hydrocarbons (PAHs). A typical representative compound of PAHs, 7,12-Dimethylbenz[a]anthracene (DMBA), was used to induce rat breast cancer. The results showed that therapeutic concentration of VPA (50 and 100 mg/kg) delayed the occurrence of tumors, reduced tumor formation rate and attenuated tumors growth, and have a protective effect on normal tissues. The macrophage-mediated inflammatory response was found to be associated with the observed effect of VPA. In addition, we screened and validated a possible gene, Sema3c, which was involved in DMBA-induced breast cancer development and can be inhibited by VPA.

Keywords: DMBA; Sema3c; breast tumor; macrophage; valproic acid (VPA).