The no-observed-adverse-effect level of phthalates promotes proliferation and cell cycle progression in normal human breast cells

Fang Ping Chen*, Mei Hua Chien, Chun Hui Lee

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

Abstract

Objective: The data on the association between phthalates and breast cancer risk remains inconsistent. This study aimed to explore the possible mechanism of low-dose exposures of phthalates, including Butyl benzyl phthalate (BBP), di(n-butyl) phthalate (DBP), and di(20ethylhexyl) phthalate (DEHP), on breast tumorigenesis. Methods and methods: MCF-10A normal breast cells were treated with phthalates (10 and 100 nM) and 17β-estradiol (E2, 10 nM), which were co-cultured with fibroblasts from normal mammary tissue. Cell viability, cycle, and apoptosis were detected by MTT assay, flow cytometry, and TUNEL assay respectively. The expression levels of related proteins were determined by Western blot. Results: Like E2, both 10 nM and 100 nM phthalates exerted significantly higher cell viability, lower apoptosis, and increased cell numbers in the S and G2/M phases with up-regulation of cyclin D/CDK4, cyclin E/CDK2, cyclin A/CDK2, cyclin A/CDK1, and cyclin B/CDK1, compared with the control group. Significant increase in PDK1, P13K, p-AKT, p-mTOR, and BCL-2 expression and a decrease in Bax protein, cytochrome C, caspase 8, and caspase 3 levels were noted in cells treated with 10 nM and 100 nM phthalates and E2, compared with the control group and MCF-10A cells co-cultured with fibroblasts. The effects of the three phthalates were noted to be dose-dependent. Conclusions: The results indicate that phthalates at a level below its no-observed-adverse-effect concentration, as defined by the current standards, still induce cell cycle progression and proliferation as well as inhibit apoptosis of normal breast cells. Thus, the possibility of breast tumorigenesis through chronic phthalate exposure should be considered.

Original languageEnglish
Pages (from-to)874-883
Number of pages10
JournalTaiwanese Journal of Obstetrics and Gynecology
Volume62
Issue number6
DOIs
StatePublished - 11 2023

Bibliographical note

Publisher Copyright:
© 2023

Keywords

  • Breast tumorigenesis
  • Butyl benzyl phthalate
  • Di(20ethylhexyl) phthalate
  • Di(n-butyl) phthalate
  • MCF-10A normal breast cells

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