Figure 5. Vilazodone and sertraline target the sphere-forming tumor cell subpopulation and BTIC by an irreversible mechanism.

(a) Exposure of HCC1954 breast tumor cells to vilazodone in a primary sphere-forming assay (left-most panel) irreversibly reduced the frequency of sphere-forming cells in secondary sphere-forming assays performed in drug-free medium (right-most panel). (b) Exposure of HCC1954 tumor cells to sertraline in a primary sphere-forming assay irreversibly reduced the frequency of sphere-forming cells in secondary sphere-forming assays carried out in the absence of the drug. (c) Sertraline targets HCC1954 breast tumor-initiating cells. Dispersed HCC1954 cells from tumorspheres exposed to sertraline under sphere-forming conditions ex vivo, yield tumors after transplant into NOD/SCID mice with an increased latency and at a reduced frequency compared to tumor cells exposed to the vehicle. Mice were monitored for disease-free survival by Kaplan-Meier survival analysis and statistical significance was determined using a log-rank (Mantel-Cox) test: P = 3.0 × 10⁻⁴.