Triphenyl Phosphate Activates Estrogen Receptor α/NF-κB/ Cyclin D1 Signaling To Stimulate Cell Cycle Progression in Human Ishikawa Endometrial Cancer Cells

Authors

Hyun Young Kwon
Seung Bin Park
Myoungseok Han
Jung-Woo Park
Yongmin Lee
Sang Jun Han
Youngmin Kwon
Yeon Jean Cho

Publication Date

11-1-2022

Journal

Obstetrics & Gynecology Science

DOI

10.5468/ogs.22108

PMID

36254600

PMCID

PMC9683935

PubMedCentral® Posted Date

8-4-2022

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes

Keywords

Triphenyl phosphate, Estrogen receptor, Cyclin D1, Cell cycle, Human Ishikawa endometrial cancer cells

Abstract

OBJECTIVE: Triphenyl phosphate (TPHP) is one of the most commonly used organophosphorus flame retardants that may accumulate in the environment. However, its effects on human reproductive organs have not been well studied. We aimed to investigate the in vitro effects of TPHP in human Ishikawa endometrial cancer cells to elucidate how TPHP exposure disrupts intracellular signaling and cell proliferation in reproductive tissues.

METHODS: Human Ishikawa endometrial cancer cells were exposed to TPHP.

RESULTS: Exposure to TPHP elevated the levels of estrogen receptor (ER) α and progesterone receptor-B and reduced ER β in human Ishikawa endometrial cancer cells. TPHP stimulated phosphoinositide 3-kinase/protein kinase B and mitogenactivated protein kinase/ extracellular signal-regulated kinases 1/2 kinase signaling, which may contribute to the activation of ER function and induce nuclear translocation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) in human Ishikawa endometrial cancer cells. Activated ER and NF-κB stimulate the expression of cyclin D1/ cyclin-dependent kinase (CDK) 4/CDK6, indicating cell cycle progression and proliferation.

CONCLUSION: This report may provide new information on the molecular mechanisms underlying how TPHP exposure dysregulates the cellular physiology of the human endometrium.