Characterising the effect of sodium channel inhibitors on viability and intracellular sodium content in triple-negative breast cancer cells

In cancers such as triple-negative breast cancer (TNBC), intracellular sodium (Na+) concentration is increased in tumours compared to healthy tissues. This physiological change is associated with an upregulation of Na+ channels in cancer cells. Increased expression of these Na+ channels is correlated with key hallmarks of cancer progression such as invasion, proliferation, and inflammation. Due to the involvement of Na+ channels in these crucial mechanisms of cancer, they may be viable therapeutic targets. However, the contribution of these various Na+ transport mechanisms to pathways regulating intracellular Na+, and consequent cell survival, proliferation, and invasion in TNBC is still underexplored. The hypothesis is that the viability of TNBC cells, and their intracellular Na+, is regulated by multiple Na+ channels. This was tested by evaluating the effect of Na+ channel inhibitors on viability, intracellular Na+ and Ca2+. Dronedarone and ouabain both exhibited a significant effect on reducing the viability of TNBC cells whilst decreasing and increasing the intracellular Na+ respectively. Additionally, dronedarone increased intracellular Ca2+ in a mechanism partially dependent on the Ca2+ stores of the endoplasmic reticulum. Further experiments would be required to fully understand whether dronedarone’s mechanism of action on TNBC cells is Na+-dependent.