Particular sensitivity to calcium channel blockers of the fast inward voltage-dependent sodium current involved in the invasive properties of a metastastic breast cancer cell line.
1. A voltage-dependent sodium current has been described in the highly invasive breast cancer cell line MDA-MB-231. Its activity is associated with the invasive properties of the cells. The aim of our study was to test whether this current (I(Na)) is sensitive to three representative calcium channel blockers: verapamil, diltiazem and nifedipine. I(Na) was studied in patch-clamp conditions. 2. I(Na) was sensitive to verapamil (IC(50)=37.6+/-2.5 microM) and diltiazem (53.2+/-3.6 microM), while it was weakly sensitive to nifedipine. 3. The tetrodotoxin (TTX) concentration, which fully blocks I(Na) (30 microM), did not affect cell proliferation. Diltiazem and verapamil, at concentrations that do not fully block I(Na), strongly reduced cell proliferation, suggesting, regarding proliferation, that these molecules act on targets distinct from sodium channels. These targets are probably not other ionic channels, since the current measured at the end of a 500 ms long pulse in the voltage range between -60 and +40 mV was unaffected by verapamil and diltiazem. 4. We conclude that the sodium channel expressed in MDA-MB-231 cells is sensitive to several calcium channel blockers. The present study also underlines the danger of concluding to the possible involvement of membrane channel proteins in any phenomenon on the sole basis of pharmacology, and without an electrophysiological confirmation.
Roger
Sébastien
S
Nutrition, Croissance et Cancer, Emi-U 0211, Faculté de Médecine, 2 Bd Tonnellé, Tours 37032, France.
Le Guennec
Jean-Yves
JY
Besson
Pierre
P
D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004110:Diltiazem / Q000494:pharmacology; D004594:Electrophysiology; D005260:Female; D006801:Humans; D009543:Nifedipine / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015222:Sodium Channels / Q000187:drug effects / Q000378:metabolism*; D019789:Tetraethylammonium / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology
D002121:Calcium Channel Blockers; D026902:Potassium Channel Blockers; D015222:Sodium Channels; D013779:Tetrodotoxin; D019789:Tetraethylammonium; D014700:Verapamil; D004110:Diltiazem; D009543:Nifedipine