Anti-hypertensive Calcium-Blocking Drugs Induce a Change in Viscoelasticity of Mcf-7 Cancer Cells

2020 
In this work, we studied the effect of common calcium channel blockers (Verapamil Hydrochloride and Nifedipine, usually prescribed for cardiovascular diseases) on the viscoelastic property of both tumorigenic (MCF-7) and vascular endothelial (HUVEC) cell-line. Specifically, an optical-tweezer was used to locally "press-down" on the cell membrane. Fluctuations of optically-trapped dielectric beads attached to the cell membrane were measured to study the effect of drugs on the mechanical properties of the membrane and the cytoskeleton. We observed that MCF-7 cells exhibit a significantly higher mean squared displacement (MSD) in response to these drugs as compared to HUVEC cells, under no-compression condition. Furthermore, optically induced compression of cell-membrane induced a significant drop in MSD of MCF-7 cells, whereas HUVEC cells showed a significant rise in MSD. To further test these results, we depolymerized actin-cytoskeleton using latrunculin-B and measured fluctuations of beads on the surface of cells. Immunofluorescence imaging of the actin cytoskeleton correlates with the variation in the viscoelastic response of MCF-7 and HUVEC under the influence of these drugs. Our power-spectrum analysis at 10 Hz shows that actin-depolymerization decreased the activity of both cell types; however, cells treated with nifedipine or verapamil showed contrasting effects. Together, these results show that clinically approved calcium-ion blocking cardiovascular drugs have a significant effect on the viscoelastic properties of circulating tumor cells in the blood.
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