Phthalate plasticizer di(2-ethyl-hexyl) phthalate induces cyclooxygenase-2 expression in gastric adenocarcinoma cells

Jhen Hong Wong, Yu Shiuan Wang, Sean Nam, Kuo Hao Ho, Che Mai Chang, Ku Chung Chen, Yi Fan Chen, Wei Chiao Chang

Research output: Contribution to journalArticle

Abstract

The phthalate plasticizer, di(2-ethyl-hexyl) phthalate (DEHP), and its derived metabolites are common anthropogenic environmental toxins, which are known to act as endocrine disruptors. Numerous studies have associated DEHP with disruption of sex hormones, abnormal development of reproductive organs, allergies, and inflammation. Its role in promoting inflammation has been reported by both human epidemiological and animal studies. In stomach tissue, chronic inflammation is known to accompany mucosal damage, and pave the way to gastritis, stomach ulcers, and ultimately gastric cancer. Eastern Asian populations possess the highest gastric cancer incidences in the world. Coincidentally, East Asia is one of the world's major sites for plastics manufacture and export. Thus, possible correlations between DEHP, a common plasticizer, and gastric cancer are of great interest. Our study revealed several critical findings. First, even at very low dosage, mimicking the residual plasticizer exposure, detrimental effects of DEHP on gastric cells can be detected. Second, gastric cells treated with DEHP increased cyclooxygenase-2 (COX-2) in a time-dependent manner. Third, promoter deletion studies revealed a critical role of nuclear factor-kappa B (NF-κB) for COX-2 gene responses. Finally, our results indicated that a low concentration of DEHP is able to trigger COX-2 activation via the extracellular signal–regulated kinase (ERK1/2) and NF-κB signaling pathway. Taken together, we demonstrate that very low doses of DEHP enhance the expression of the prototypical inflammatory gene, COX-2, in gastric cancer cells via ERK1/2 and NF-κB activation. This study provides important insights into the inflammatory process and damages associated with phthalate plasticizers exposure.

Original languageEnglish
JournalEnvironmental Toxicology
DOIs
Publication statusPublished - Jan 1 2019

Fingerprint

Plasticizers
phthalate
Cyclooxygenase 2
Stomach
Adenocarcinoma
Stomach Neoplasms
NF-kappa B
cancer
Inflammation
Genes
Chemical activation
sex hormone
Allergies
phthalic acid
Endocrine Disruptors
allergy
damage
Mitogen-Activated Protein Kinase 3
endocrine disruptor
Far East

Keywords

  • COX-2
  • DEHP
  • gastric cancer cells
  • inflammation

ASJC Scopus subject areas

  • Toxicology
  • Management, Monitoring, Policy and Law
  • Health, Toxicology and Mutagenesis

Cite this

Phthalate plasticizer di(2-ethyl-hexyl) phthalate induces cyclooxygenase-2 expression in gastric adenocarcinoma cells. / Wong, Jhen Hong; Wang, Yu Shiuan; Nam, Sean; Ho, Kuo Hao; Chang, Che Mai; Chen, Ku Chung; Chen, Yi Fan; Chang, Wei Chiao.

In: Environmental Toxicology, 01.01.2019.

Research output: Contribution to journalArticle

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