Options
Saumendra K Bajpai
Loading...
Preferred name
Saumendra K Bajpai
Official Name
Saumendra K Bajpai
Alternative Name
Bajpai, Saumendra Kumar
Bajpai, Saumendra
Bajpai, Saumendra K.
Main Affiliation
Email
ORCID
Scopus Author ID
Google Scholar ID
2 results
Now showing 1 - 2 of 2
- PublicationAnti-hypertensive Calcium-Blocking Drugs Induce a Change in Viscoelasticity of Mcf-7 Cancer Cells(15-09-2020)
;Vaibavi, S. R. ;Vaippully, Rahul; 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. - PublicationCalcium-channel-blockers exhibit divergent regulation of cancer extravasation through the mechanical properties of cancer cells and underlying vascular endothelial cells(01-03-2022)
;Vaibavi, S. R. ;Sivasubramaniapandian, Manoj ;Vaippully, Rahul ;Edwina, Privita; Cardiovascular and cancer illnesses often co-exist, share pathological pathways, and complicate therapy. In the context of the potential oncological role of cardiovascular-antihypertensive drugs (AHD), here we examine the role of calcium-channel blocking drugs on mechanics of extravasating cancer cells, choosing two clinically-approved calcium-channel blockers (CCB): Verapamil-hydrochloride and Nifedipine, as model AHD to simultaneously target cancer cells (MCF7 and or MDA231) and an underlying monolayer of endothelial cells (HUVEC). First, live-cell microscopy shows that exposure to Nifedipine increases the spreading-area, migration-distance, and frequency of transmigration of MCF-7 cells through the HUVEC monolayer, whereas Verapamil has the opposite effect. Next, impedance-spectroscopy shows that for monolayers of either endothelial or cancer cells, Nifedipine-treatment alone decreases the impedance of both cases, suggesting compromised cell-cell integrity. Furthermore, upon co-culturing MCF-7 on the HUVEC monolayers, Nifedipine-treated MCF-7 cells exhibit weaker impedance than Verapamil-treated MCF-7 cells. Following, fluorescent staining of CCB-treated cytoskeleton, focal adhesions, and cell-cell junction also indicated that Nifedipine treatment diminished the cell-cell integrity, whereas verapamil treatment preserved the integrity. Since CCBs regulate intracellular Ca2+, we next investigated if cancer cell’s exposure to CCBs regulates calcium-dependent processes critical to extravasation, specifically traction and mechanics of plasma membrane. Towards this end, first, we quantified the 2D-cellular traction of cells in response to CCBs. Results show that exposure to F-actin depolymerizing drug decreases traction stress significantly only for Nifedipine-treated cells, suggesting an actin-independent mechanism of Verapamil activity. Next, using an optical tweezer to quantify the mechanics of plasma membrane (PM), we observe that under constant, externally-applied tensile strain, PM of Nifedipine-treated cells exhibits smaller relaxation-time than Verapamil and untreated cells. Finally, actin depolymerization significantly decreases MSD only for Verapamil treated cancer-cells and endothelial cells and not for Nifedipine-treated cells. Together, our results show that CCBs can have varied, mechanics-regulating effects on cancer-cell transmigration across endothelial monolayers. A judicious choice of CCBs is critical to minimizing the pro-metastatic effects of antihypertension therapy.