Figure 4.

(A) Dilazep suppresses the c-MYC transcriptional program. Using GSEA, we compared our signatures of dilazep treatment in our three PC cell lines against publicly available prostate-specific signatures of c-MYC activity. We found that the gene programs induced by c-MYC are strongly suppressed by dilazep in all three cell lines for, while genes suppressed by c-MYC are strongly induced by dilazep. These results demonstrate that dilazep potently suppresses c-MYC activity in PC cells. All P < 0.001. (B) The dilazep transcriptional program correlates with decreased GATA2 activity score, AR activity score, and c-MYC activity score in PC patient cohorts. We applied the gene signature derived from our treatment of LNCaP cells with dilazep, as well as the previously published footprints of GATA2 (GSE63539 and He et al. 2014), AR (GSE63539 and He et al. 2014) and c-MYC (two signatures, one from overexpression of c-MYC for 12 hrs in LNCaP cells (GSE51384 and Barfeld et al. 2015) and the other from knockdown of c-MYC via siRNA in LNCaP (Koh et al. 2011)), and computed an activity score for each specimen in multiple previously reported human PC specimen cohorts: Taylor et al. (2010), Cai et al. (2013), and the Cancer Genome Atlas (TCGA) (https://doi.org/10.1530/ERC-21-0085.