Fig. 5.

Specific HDAC isoforms target chemotherapy-acquired CSL state. The FACS mean values of ALDH and CD44 in live populations, CSL/Live, CSL/Total, and viability for CSL reversal drugs screening were expressed in heat maps for CAMA-1 (A) and MDA-MB-231 (B) cell lines. Cells were cultured in medium (3D) and treated for 72 h with doxorubicin (0.1 µM for CAMA-1, 0.5 µM for MDA-MB-231), carboplatin (50 µM for all cell lines), and paclitaxel (1 µM for all cell lines), and then treated with specific HDAC isoforms inhibitors as indicated doses for 72 h before ALDEFLUOR/CD44 staining. The vehicle controls (DMSO+DMSO) were set as fold one. All the other chemotherapy plus DMSO/inhibitor combinations were expressed as the fold change relative to the controls. The Chemo plus DMSO served as the positive controls. The mean values of triplicate tests were showed with color indicated as the legends. In heat maps of ALDH, CD44, CSL/Live, and CSL/Total, # is chemo plus DMSO significantly higher (p<0.05) than no treatment control, and in heat maps of viability, # is chemo plus DMSO significantly lower (p<0.05) than no treatment control. In all heat maps, * is chemo plus inhibitor significantly lower (p<0.05) than chemo plus DMSO. The potential specific HDAC isoforms inhibitors target to CSL cells are highlighted with red blocks as its reversal effect for both ALDH and CD44.