Tamoxifen inhibits acidification in cells independent of the estrogen receptor. Academic Article uri icon

Overview

abstract

  • Tamoxifen has been reported to have numerous physiological effects that are independent of the estrogen receptor, including sensitization of resistant tumor cells to many chemotherapeutic agents. Drug-resistant cells sequester weak base chemotherapeutics in acidic organelles away from their sites of action in the cytosol and nucleus. This work reports that tamoxifen causes redistribution of weak base chemotherapeutics from acidic organelles to the nucleus in drug-resistant cells. Agents that disrupt organelle acidification (e.g., monensin, bafilomycin A1) cause a similar redistribution. Measurement of cellular pH in several cell lines reveals that tamoxifen inhibits acidification of endosomes and lysosomes without affecting cytoplasmic pH. Similar to monensin, tamoxifen decreased the rate of vesicular transport though the recycling and secretory pathways. Organellar acidification is required for many cellular functions, and its disruption could account for many of the side effects of tamoxifen.

publication date

  • April 13, 1999

Research

keywords

  • Anti-Bacterial Agents
  • Endosomes
  • Hydrogen-Ion Concentration
  • Lysosomes
  • Macrolides
  • Monensin
  • Receptors, Estrogen
  • Tamoxifen

Identity

PubMed Central ID

  • PMC16349

Scopus Document Identifier

  • 0033551150

Digital Object Identifier (DOI)

  • 10.1073/pnas.96.8.4432

PubMed ID

  • 10200279

Additional Document Info

volume

  • 96

issue

  • 8