Expression of estrogen-, progesterone-, and androgen-responsive genes in MCF-7 and MDA-MB-231 cells treated with o,p'-DDT, p,p'-DDT, or endosulfan

J Biochem Mol Toxicol. 2021 Jun;35(6):1-8. doi: 10.1002/jbt.22773. Epub 2021 Mar 16.

Abstract

Endocrine disruptors are a major concern due to their possible association with hormone-dependent carcinogenesis. Some examples of compounds with such properties are organochlorine pesticides (OCPs). OCPs are persistent pollutants with high lipophilicity, long half-life, and bioaccumulation potential. In the past, some of the most commonly used OCPs were dichlorodiphenyltrichloroethane (DDT) and endosulfan. Here, we investigated the effects of o,p'-DDT, p,p'-DDT, and endosulfan and of hormones estradiol, testosterone, and progesterone on the expression of estrogen, progesterone, and androgen receptors (ER, PR, and AR) and of their target genes (KLF4, VEGFA, CCND1, PRLR, CDKN1A, and BCL6) in MCF-7 and MDA-MB-231 cells. The results confirmed that under the action of the insecticides, there are dose- and time-dependent changes in the expression of these receptors and target genes. As corroborated by an experiment with ER, PR, and AR negative MDA-MB-231 cells, the change in the expression of KLF4, VEGFA, CCND1, and PRLR in MCF-7 cells treated with o,p'-DDT and the change in CDKN1A and PRLR expression in MCF-7 cells treated with p,p'-DDT are likely mediated by ER, PR, and AR pathways. In conclusion, we have identified some targets of DDT and endosulfan and confirmed that the effects of insecticides on the expression of these target genes differ for breast cancer cell lines with different receptor statuses.

Keywords: dichlorodiphenyltrichloroethane; endocrine disruptors; endosulfan; hormone receptors.

MeSH terms

  • Androgens / pharmacology*
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • DDT / pharmacology*
  • Endocrine Disruptors
  • Endosulfan / pharmacology*
  • Estrogens / pharmacology*
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Humans
  • Kruppel-Like Factor 4
  • MCF-7 Cells
  • Neoplasm Proteins / biosynthesis*
  • Progesterone / pharmacology*

Substances

  • Androgens
  • Endocrine Disruptors
  • Estrogens
  • KLF4 protein, human
  • Kruppel-Like Factor 4
  • Neoplasm Proteins
  • Progesterone
  • DDT
  • Endosulfan