Non-anti-mitotic concentrations of taxol reduce breast cancer cell invasiveness |
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Authors: | Truong-An Tran Ludovic Gillet Sébastien Roger Pierre Besson Edward White |
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Institution: | a Inserm, U921, 37000 Tours, France b Université François-Rabelais, 37000 Tours, France c Institute of Membrane and Systems Biology, University of Leeds, LS2 9JT LEEDS, UK |
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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 (NaV) are abnormally expressed in the highly metastatic breast cancer cell line MDA-MB-231 and not in MDA-MB-468 cell line. Inhibiting NaV 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. NaV 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 NaV, at low doses that have no effect on cell proliferation. This effect might be due to a modulation of signalling pathways involving sodium channels. |
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Keywords: | Taxol Tubulin Cancer invasiveness NaV1 5 Metastasis MDA-MB-231 MDA-MB-468 |
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