Figure 4

Identification of BKM120 as a CD44⁺/CD24⁻ TIC-targeting drug. (A) Screen of a panel of clinically used drugs identified BKM120, a pan- PI3K inhibitor, as a potent CD44⁺/CD24⁻ cell targeting drug in MDA-MB231 cells. (B) BKM120 showed dose-dependent effects in decreasing CD44⁺/CD24⁻ (left panel) but not ALDH⁺ (right panel) TIC populations in MDA-MB231 cells. MDA-MB231 cells reated with 5 µM, 15 µM and 30 µM BKM120 for 24 hours were analyzed for TIC population with FACS. (C) BKM120 showed time-dependent effects in decreasing CD44⁺/CD24⁻ (left panel) but not ALDH⁺ (right panel) TIC populations in SUM102 cells. SUM102 cells were treated with 15 μM BKM120 for 24 hour or 48 hours were analyzed for TIC population with FACS. (D) BKM120 showed a time-dependent effect in inhibiting tumorsphere formation in MDA-MB231 cells. For panel (A–D), one-way ANOVA followed by multiple comparisons was used with P < 0.05 as statistically significant. (E) Results of limiting dilution analysis for secondary sphere formation of MDA-MB231 cells with and without BKM120 treatment. Data were analyzed using the ELDA software. *Indicates significant difference from untreated group by BKM120. Pr = 2.14 × 10⁻⁶.