Non-anti-mitotic concentrations of taxol reduce breast cancer cell invasiveness.
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.
Tran
Truong-An
TA
Inserm, U921, 37000 Tours, France.
Gillet
Ludovic
L
Roger
Sébastien
S
Besson
Pierre
P
White
Edward
E
Le Guennec
Jean-Yves
JY
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D008938:Mitosis / Q000187:drug effects; D062554:NAV1.5 Voltage-Gated Sodium Channel; D009361:Neoplasm Invasiveness; D017239:Paclitaxel / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D015222:Sodium Channels / Q000187:drug effects; D050257:Tubulin Modulators / Q000494:pharmacology*
D000972:Antineoplastic Agents, Phytogenic; D062554:NAV1.5 Voltage-Gated Sodium Channel; C568320:SCN5A protein, human; D015222:Sodium Channels; D050257:Tubulin Modulators; D017239:Paclitaxel