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Live Imaging to Study Microtubule Dynamic Instability in Taxane-resistant Breast Cancers
Published on: February 20, 2017
Non-anti-mitotic concentrations of taxol reduce breast cancer cell invasiveness
Truong-An Tran1, Ludovic Gillet, Sébastien Roger
1Inserm, 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.
Insights
Low-dose Taxol reduces breast cancer cell invasion by modulating voltage-dependent sodium channels (Na(V)), independent of proliferation inhibition. This suggests novel therapeutic strategies targeting Na(V) in metastatic breast cancer.
Area of Science:
- Oncology
- Cell Biology
- Pharmacology
Background:
- Taxol (paclitaxel) is a cornerstone chemotherapy for breast cancer, primarily known for its anti-mitotic effects.
- However, microtubule-targeting agents also exhibit antimetastatic properties not fully explained by proliferation inhibition.
- Voltage-dependent sodium channels (Na(V)) are implicated in cancer cell invasiveness, notably in the MDA-MB-231 breast cancer cell line.
Purpose of the Study:
- To investigate the effect of low-dose Taxol on the invasiveness and migration of breast cancer cell lines MDA-MB-231 and MDA-MB-468.
- To determine if Taxol's antimetastatic effects are linked to voltage-dependent sodium channel activity.
Main Methods:
- Treatment of MDA-MB-231 and MDA-MB-468 cells with 10 nM Taxol for 2 hours.
- Assessment of cell proliferation, migration (transwell assay), and invasion.
- Electrophysiological recordings (patch-clamp) to measure Na(V) channel activity.
- Co-application of Taxol and tetrodotoxin (a Na(V) inhibitor).
Main Results:
- Low-dose Taxol (10 nM) significantly reduced MDA-MB-231 cell invasion by 40% without affecting proliferation or migration.
- Taxol pre-treatment altered Na(V) channel activity in MDA-MB-231 cells.
- No additive effect was observed when Taxol and tetrodotoxin were used together, suggesting a shared pathway.
Conclusions:
- Taxol exhibits anti-invasive effects at low doses that do not inhibit proliferation, particularly in Na(V)-expressing cancer cells.
- These low-dose anti-tumoral effects may involve the modulation of signaling pathways associated with sodium channels.
- This highlights a potential therapeutic strategy targeting Na(V) channels in metastatic breast cancer.
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