Effects of bisphenol A on the proliferation, migration, and tumor growth of colon cancer cells: In vitro and in vivo evaluation with mechanistic insights related to ERK and 5-HT3

Ji Hae Jun, Ju Eun Oh, Jae Kwang Shim, Young Lan Kwak, Jin Sun Cho

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)

Abstract

Bisphenol A (BPA) is a well-known endocrine-disrupting chemical related to the carcinogenesis of estrogen-responsive organs. Although human exposure to BPA mainly occurs via the oral route, its association with colon cancer has not been fully elucidated. We investigated the effects of BPA on the proliferation, migration, and tumor growth of colon cancer cells. BPA significantly promoted the proliferation of HT-29 human colon adenocarcinoma cells in a time- and dose-dependent manner. BPA also increased HT-29 cells migration. BPA increased the phosphorylation of extracellular signal-regulated kinase (ERK), and inhibition of the ERK pathway attenuated BPA-induced proliferation and migration. In addition, BPA reduced E-cadherin expression, a key factor impeding epithelial-to-mesenchymal transition, and increased 5-HT3 receptors expression, a major mitogenic factor. In xenograft models, tumor volume of the BPA-treated nude mice was 4.6 times that of the saline-treated group. Our findings provide primary evidence regarding the link between BPA and human colon cancer by demonstrating that BPA promotes the proliferation, migration, and tumor growth of colon cancer cells in both in vitro and in vivo models. In addition, we provided the mechanism of action of BPA, involved in the activation of the ERK pathway, the decrease in E-cadherin, and the increase in 5-HT3 receptors.

Original languageEnglish
Article number112662
JournalFood and Chemical Toxicology
Volume158
DOIs
Publication statusPublished - 2021 Dec

Bibliographical note

Funding Information:
This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (No. 2017R1C1B5018102 ).

Publisher Copyright:
© 2021 Elsevier Ltd

All Science Journal Classification (ASJC) codes

  • Food Science
  • Toxicology

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