Anticancer Drug Tamoxifen Affects Catecholamine Transmitter Release and Storage from Single Cells

Zahra Taleat, Anna Larsson, Andrew G. Ewing

Research output: Contribution to journalArticlepeer-review

Abstract

Electrochemical measurements of exocytosis combined with intracellular vesicle impact electrochemical cytometry have been used to evaluate the effect of an anticancer drug, tamoxifen, on catecholamine release at the single-cell level. Tamoxifen has been used for over 40 years to treat estrogen receptor-positive breast cancers during both early stages of the disease and in the adjuvant setting. Tamoxifen causes memory and cognitive dysfunction, but the reasons for the cognitive impairment and memory problems induced by this anticancer drug are not well-known. We show that tamoxifen, through a nongenomic mechanism, can modulate both exocytosis and vesicle catecholamine storage in a model cell line. The results indicate that exocytosis is inhibited at high concentrations of tamoxifen and is stimulated at low levels. Tamoxifen also elicits a significant concentration-dependent change in total catecholamine content of single vesicles, while sub-nanomolar concentrations of the drug have stimulatory activity on the catecholamine content of vesicles. In addition, it has profound effects on storage at higher concentrations. Tamoxifen also reduces the intracellular free Ca2+ but only at micromolar concentration, by acting on voltage-gated Ca2+ channels, which likely affects neurotransmitter secretion.

Original languageEnglish (US)
Pages (from-to)2060-2069
Number of pages10
JournalACS Chemical Neuroscience
Volume10
Issue number4
DOIs
StatePublished - Apr 17 2019

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Physiology
  • Cognitive Neuroscience
  • Cell Biology

Fingerprint Dive into the research topics of 'Anticancer Drug Tamoxifen Affects Catecholamine Transmitter Release and Storage from Single Cells'. Together they form a unique fingerprint.

Cite this