Non-anti-mitotic concentrations of taxol reduce breast cancer cell invasiveness

Biochem Biophys Res Commun. 2009 Feb 6;379(2):304-8. doi: 10.1016/j.bbrc.2008.12.073. Epub 2008 Dec 26.

Abstract

Taxol is widely used in breast cancer chemotherapy. Its effects are primarily attributed to its anti-mitotic activity. Microtubule perturbators also exert antimetastatic activities which cannot be explained solely by the inhibition of proliferation. Voltage-dependent sodium channels (Na(V)) are abnormally expressed in the highly metastatic breast cancer cell line MDA-MB-231 and not in MDA-MB-468 cell line. Inhibiting Na(V) activity with tetrodotoxin is responsible for an approximately 0.4-fold reduction of MDA-MB-231 cell invasiveness. In this study, we focused on the effect of a single, 2-h application of 10 nM taxol on the two cell lines MDA-MB-231 and MDA-MB-468. At this concentration, taxol had no effect on proliferation after 7 days and on migration in any cell line. However it led to a 40% reduction of transwell invasion of MDA-MB-231 cells. There was no additive effect when taxol and tetrodotoxin were simultaneously applied. Na(V) activity, as assessed by patch-clamp, indicates that it was changed by taxol pre-treatment. We conclude that taxol can exert anti-tumoral activities, in cells expressing Na(V), at low doses that have no effect on cell proliferation. This effect might be due to a modulation of signalling pathways involving sodium channels.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Breast Neoplasms / pathology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Humans
  • Mitosis / drug effects
  • NAV1.5 Voltage-Gated Sodium Channel
  • Neoplasm Invasiveness
  • Paclitaxel / pharmacology*
  • Signal Transduction / drug effects
  • Sodium Channels / drug effects
  • Tubulin Modulators / pharmacology*

Substances

  • Antineoplastic Agents, Phytogenic
  • NAV1.5 Voltage-Gated Sodium Channel
  • SCN5A protein, human
  • Sodium Channels
  • Tubulin Modulators
  • Paclitaxel