Effect of Mono-2-ethyhexyl Phthalate on DNA Methylation in Human Prostate Cancer LNCaP Cells.

Jian Hui WU; Jiao CHEN; Yong WANG; Bin XIA; Rong WANG; Yan ZHAO; Qin Xia WANG; Qi SONG; Shun Heng YAO; Yun Hui ZHANG; Zu Yue SUN

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Effect of Mono-2-ethyhexyl Phthalate on DNA Methylation in Human Prostate Cancer LNCaP Cells.

Author: Jian Hui WU ^{1
,

2
,

3} ; Jiao CHEN ⁴ ; Yong WANG ¹ ; Bin XIA ⁵ ; Rong WANG ¹ ; Yan ZHAO ⁵ ; Qin Xia WANG ¹ ; Qi SONG ⁵ ; Shun Heng YAO ¹ ; Yun Hui ZHANG ⁵ ; Zu Yue SUN ¹ ;
Author Information

1. National Evaluation Centre for the Toxicology of Fertility Regulating Drug, Department of Pharmacology and Toxicology, Shanghai Institute of Planned Parenthood Research, Shanghai 200032, China
2. Key Laboratory of Reproduction Regulation of NPFPC, Shanghai 200032, China
3. Reproductive and Developmental Research Institute of Fudan University, Shanghai, Shanghai 200032, China.
4. Division of Health Risk Factors Surveillance and Control, Shanghai Municipal Center for Disease Control and Prevention, Shanghai 200336, China
5. Key Laboratory of Public Health Safety, Ministry of Education, School of Public Health, Fudan University, Shanghai 200032, China.
Publication Type:Journal Article
Keywords: Genomic; LNCaP; Methylation; Mono (2-ethyhexyl) phthalate; PTCH; SMO
MeSH: Antineoplastic Agents; chemistry; pharmacology; Cell Line, Tumor; DNA Methylation; Humans; Male; Phthalic Acids; chemistry; Prostatic Neoplasms; metabolism
From: Biomedical and Environmental Sciences 2017;30(9):641-648
CountryChina
Language:English
Abstract:
OBJECTIVETo evaluate whether mono (2-ethylhexyl) phthalate (MEHP) affects genomic DNA methylation and the methylation status of some specific genes such as patched gene (PTCH) and smoothened gene (SMO) in LNCaP cells.
METHODSLNCaP cells were treated with MEHP (0, 1, 5, 10, and 25 μmol/L) for 3 days. An ELISA assay was preformed to detect genomic methylation, including 5-methylcytosine (5-mC) and 5-hydroxymethylcytosine (5-hmC) content. A pyrosequencing assay was applied to assess DNA methylation in PTCH and SMO gene promoters. The correlation between DNA methylation and gene expression was assessed.
RESULTSThe proportion of cytosines with 5-mC methylation in LNCaP cells was significantly decreased by MEHP (1, 5, 10, and 25 μmol/L) in a dose-dependent manner (P < 0.01). For genes in the Hedgehog pathway, there was no significant MEHP concentration-dependent difference in the DNA methylation of PTCH and SMO.
CONCLUSIONMEHP might affect the progression of prostate cancer through its effect on global DNA methylation.