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

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

Author information

1
Inserm, U921, 37000 Tours, France.

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.

PMID:
19111674
DOI:
10.1016/j.bbrc.2008.12.073
[Indexed for MEDLINE]

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