Docosahexaenoic acid (omega-3) blocks voltage-gated sodium channel activity and migration of MDA-MB-231 human breast cancer cells.
Omega-3 polyunsaturated fatty acids have been suggested to play an important role in cancer prevention/progression, on the one hand, and in modulation of membrane ion channels on the other. We investigated whether docosahexaenoic acid would influence the in vitro migration of MDA-MB-231 human breast cancer cells. An important follow-up question was whether any effect would involve voltage-gated Na(+) channels, shown previously to occur in human breast cancer in vitro and in vivo and to correlate with metastatic potential. Short-term (acute) and long-term (24-72 h) application of docosahexaenoic acid suppressed the activity of the channel activity in a dose-dependent manner. At the working concentrations of docosahexaenoic acid used (0.05-0.5 microM), there was no effect on proliferation. Long-term treatment with docosahexaenoic acid down-regulated mRNA and protein (total and plasma membrane) levels of neonatal Nav1.5 voltage-gated Na(+) channel, known to be predominant in these cells. Docosahexaenoic acid suppressed migration of the MDA-MB-231 cells to the same extent as tetrodotoxin, a highly specific blocker of voltage-gated Na(+) channels, but the two effects were not additive. It was concluded that the docosahexaenoic acid-induced suppression of cellular migration occurred primarily via down-regulation of voltage-gated Na(+) channel (neonatal Nav1.5) mRNA and functional protein expression.
Isbilen
Banu
B
Neuroscience Solutions to Cancer Research Group, Division of Cell and Molecular Biology, Imperial College London, Sir Alexander Fleming Building, South Kensington Campus, London SW7 2AZ, UK.
Fraser
Scott P
SP
Djamgoz
Mustafa B A
MB
D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D004594:Electrophysiology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007231:Infant, Newborn; D015640:Ion Channel Gating / Q000187:drug effects*; D009124:Muscle Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism*; D062554:NAV1.5 Voltage-Gated Sodium Channel; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015222:Sodium Channels / Q000235:genetics / Q000378:metabolism*; D013779:Tetrodotoxin / Q000494:pharmacology
D009124:Muscle Proteins; D062554:NAV1.5 Voltage-Gated Sodium Channel; D012333:RNA, Messenger; C568320:SCN5A protein, human; D015222:Sodium Channels; D004281:Docosahexaenoic Acids; D013779:Tetrodotoxin