Benzophenone-1 and nonylphenol stimulated MCF-7 breast cancer growth by regulating cell cycle and metastasis-related genes via an estrogen receptor α-dependent pathway.

Endocrine-disrupting chemicals (EDC) are defined as environmental compounds that produce adverse health manifestations in mammals by disrupting the endocrine system. Benzophenone-1 (2,4-dihydroxybenzophenone, BP1) and nonylphenol (NP), which are discharged from numerous industrial products, are known EDC. The aim of this study was to examine the effects of BP1 and NP on proliferation and metastasis of MCF-7 human breast cancer cells expressing estrogen receptors (ER). Treatment with BP1 (10⁻⁵-10⁻⁷ M) and NP (10⁻⁶-10⁻⁷ M) promoted proliferation of MCF-7 cells similar to the positive control 17 -beta-estradiol (E2). When ICI 182,780, an ER antagonist, was co-incubated with E2, BP1, or NP, proliferation of MCF-7 cells returned to the level of a control. Addition of BP1 or NP markedly induced migration of MCF-7 cells similar to E2. To elucidate the underlying molecular mechanisms produced by these EDC, alterations in transcriptional and translational levels of proliferation and metastasis-related markers, including cyclin D1, p21, and cathepsin D, were determined. Data showed increase in expression of cyclin D1 and cathepsin D and decrease in p21 at both transcriptional and translational levels. However, BP1- or NP-induced alterations of these genes were blocked by ICI 182,780, suggesting that changes in expression of these genes may be regulated by an ERα-dependent pathway. In conclusion, BP1 and NP may accelerate growth of MCF-7 breast cancer cells by regulating cell cycle-related genes and promote cancer metastasis through amplification of cathepsin D.
AuthorsSol-Ji In, Seung-Hee Kim, Ryeo-Eun Go, Kyung-A Hwang, Kyung-Chul Choi
JournalJournal of toxicology and environmental health. Part A (J Toxicol Environ Health A) Vol. 78 Issue 8 Pg. 492-505 ( 2015) ISSN: 1528-7394 [Print] England
PMID25849766 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Benzophenones
  • Biomarkers
  • Endocrine Disruptors
  • Estrogen Receptor Antagonists
  • Estrogen Receptor alpha
  • Neoplasm Proteins
  • Phenols
  • Photosensitizing Agents
  • RNA, Messenger
  • estrogen receptor alpha, human
  • fulvestrant
  • nonylphenol
  • Estradiol
  • 2,4-dihydroxybenzophenone
  • Adenocarcinoma (chemically induced, drug therapy)
  • Benzophenones (antagonists & inhibitors, toxicity)
  • Biomarkers (metabolism)
  • Breast Neoplasms (chemically induced, drug therapy)
  • Cell Cycle (drug effects)
  • Cell Movement (drug effects)
  • Cell Proliferation (drug effects)
  • Endocrine Disruptors (chemistry, toxicity)
  • Estradiol (analogs & derivatives, pharmacology)
  • Estrogen Receptor Antagonists (pharmacology)
  • Estrogen Receptor alpha (agonists, antagonists & inhibitors, genetics, metabolism)
  • Female
  • Gene Expression Regulation, Neoplastic (drug effects)
  • Humans
  • MCF-7 Cells
  • Neoplasm Proteins (agonists, antagonists & inhibitors, genetics, metabolism)
  • Osmolar Concentration
  • Phenols (antagonists & inhibitors, toxicity)
  • Photosensitizing Agents (antagonists & inhibitors, toxicity)
  • RNA, Messenger (metabolism)

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