Breast cancer cells: Modulation by melatonin and the ubiquitin-proteasome system - A review

Jerry Vriend, Russel J Reiter

Research output: Contribution to journalReview articlepeer-review

35 Scopus citations


Melatonin inhibits human breast cancer cells stimulated with estrogen. This antiproliferative action depends on the presence of the estrogen receptor alpha (ERα) in the human MCF-7 cell line and is strictly dose-dependent. Since researchers concerned with melatonin and breast cancer have not considered the relevance of the ubiquitin-proteasome system to this research in this review we do so. The fact that the first breast cancer susceptibility gene to be identified, Brca1, functions as a ubiquitin ligase indicates that the ubiquitin-proteasome system has a role in regulating susceptibility to breast cancer. While mutations of this gene increase the incidence of breast cancer, the wild type gene suppresses estrogen-dependent transcriptional events relying on the estrogen receptor ERα. Three other ubiquitin ligases, SCFSkp2, E6AP and APC, interact directly with ERα at the ERE and AP-1 promoters of ERα target genes. Melatonin, like proteasome inhibitors, decreases estrogen-induced gene transcription. Indeed, it has been reported that melatonin specifically inhibits estrogen-induced transcription mediated by ERα at the ERE and AP1 gene promoters. Herein, we present a model in which the inhibitory action of melatonin on MCF-7 cells is mediated, directly or indirectly, by the ubiquitin-proteasome system. In this model ERα, apoptotic proteins, and cell cycle proteins, all influenced by melatonin, are substrates of key ubiquitin ligases including SCFSkp2, E6AP, and SCFB-TrCP. Since dysfunction of the ubiquitin-proteasome system is a risk factor for breast cancer, this model provides a context in which to test the clinical potential, and limitations, of melatonin and proteasome inhibitors.

Original languageEnglish (US)
Pages (from-to)1-9
Number of pages9
JournalMolecular and Cellular Endocrinology
StatePublished - Dec 5 2015


  • Breast cancer
  • Estrogen receptor
  • MCF-7
  • Melatonin
  • Ubiquitin ligase

ASJC Scopus subject areas

  • Endocrinology
  • Molecular Biology
  • Biochemistry


Dive into the research topics of 'Breast cancer cells: Modulation by melatonin and the ubiquitin-proteasome system - A review'. Together they form a unique fingerprint.

Cite this