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

Jian Hui Wu1, Jiao Chen2, Yong Wang1

  • 1National Evaluation Centre for the Toxicology of Fertility Regulating Drug, Department of Pharmacology and Toxicology, Shanghai Institute of Planned Parenthood Research, Shanghai 200032, China; Key Laboratory of Reproduction Regulation of NPFPC, Shanghai 200032, China; Reproductive and Developmental Research Institute of Fudan University, Shanghai, Shanghai 200032, China.

Biomedical and Environmental Sciences : BES
|October 31, 2017
PubMed
Abstract

Insights

Mono (2-ethylhexyl) phthalate (MEHP) exposure significantly reduced global DNA methylation in prostate cancer cells. However, MEHP did not alter the methylation of specific genes involved in the Hedgehog pathway.

Area of Science:

  • Environmental epigenetics
  • Molecular toxicology

Background:

  • Phthalates are common environmental contaminants.
  • Mono (2-ethylhexyl) phthalate (MEHP) is a primary metabolite of di(2-ethylhexyl) phthalate (DEHP).
  • Epigenetic alterations, including DNA methylation, are implicated in cancer development.

Purpose of the Study:

  • To investigate the impact of MEHP on global DNA methylation.
  • To examine the effect of MEHP on the methylation status of specific genes (PTCH and SMO) in LNCaP prostate cancer cells.

Main Methods:

  • LNCaP cells were exposed to varying concentrations of MEHP (0-25 μmol/L) for 72 hours.
  • Genomic 5-methylcytosine (5-mC) and 5-hydroxymethylcytosine (5-hmC) levels were quantified using ELISA.
  • DNA methylation of PTCH and SMO gene promoters was analyzed by pyrosequencing.

Main Results:

  • MEHP significantly decreased global 5-mC levels in LNCaP cells in a dose-dependent manner (P < 0.01).
  • No significant MEHP-induced changes in DNA methylation were observed for the PTCH and SMO gene promoters.
  • The correlation between DNA methylation and gene expression was assessed.

Conclusions:

  • MEHP exposure can alter global DNA methylation patterns in prostate cancer cells.
  • MEHP's role in prostate cancer progression may involve its influence on global DNA methylation rather than specific gene promoter methylation.
Keywords:
GenomicLNCaPMethylationMono (2-ethyhexyl) phthalatePTCHSMO

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