(A) Indicated cell lines were treated with KRIBB11 or MK-2206 for 48 hrs followed by assessment of cell viability to determine the IC50 for both inhibitors. (B) Indicated cell lines were treated with vehicle, KRIBB11 alone, MK-2206 alone, or both KRIBB11 and MK-2206 in combination at the indicated drug molar ratios for 48 hrs followed by assessment of cell viability. Combination index was calculated using Calcusyn software. (C–E) Representative individual viability assay results from (B) for indicated cell lines. F-G) BT474 and MCF7 cells were treated with vehicle, KRIBB11 alone (BT474: 2 µM; MCF7: 10 µM), MK-2206 alone (BT474: 2 µM; MCF7: 8 µM), or both KRIBB11 and MK-2206. After 48 hrs of treatment on adherent plates, cells were trypsinized, counted and subjected to the mammosphere assay (F) or flow cytometry (G) to detect the tumor initiating cell population. *Indicates significant difference (p < 0.05).