FIGURE 6:

Dependence of nuclear shape and the EFC ratio on the drug dose in a targeted screen of drugs in MDA-MB-231 breast cancer cells and PANC-1 pancreatic cancer cells. (A) For each compound, the corresponding panel plots the log of the ratio of geometric means of nuclear EFC ratios (y axis) at different doses (x axis) for that drug group to the DMSO group for a given cancer cell line (MDA-MB-231 in the green line, PANC-1 in the gray line). Cells were imaged for each treatment condition from four different wells (four technical replicates). Ratios of geometric means statistically significantly greater than 1 are displayed with blue dots; those statistically significantly less than 1 are displayed with brown dots; those not statistically significantly different from 1 are displayed with gray dots. (B) Representative nuclear shapes in MDA-MB-231 or PANC-1 cancer cells for best hits that showed improvement in both cell lines compared with vehicle control (DMSO). Overlaid image of nuclei stained with DAPI (blue) and immunostained for lamin A/C (green) are shown for the lowest tested doses that showed visual improvement of nuclei (MDA-MB-231 cells; largazole at 32 nM; FK228 at 320 pM and UNC642 at 1 uM; PANC-1 cells, largazole at 100 nM; FK228 at 3.2 nM and UNC642 at 3.2 uM). Scale bars represent 25 µm. Statistical comparisons were performed with tests of contrasts on an omnibus three-way ANOVA model (see Materials and Methods). The number of nuclei per treatment, adjusted p values and estimates of contrasts are provided in Supplemental Table S5.