Fig. 4. Combined targeting of HSF1 and CBS inhibits PCa growth.

To determine if there was an additive effect from inhibiting HSF1 and CBS, the HSF1 inhibitor SISU-102 was used to treat C4-2 (a) and PC3 (b) cells for 48 h before addition of the CBS inhibitor CH004 because we have shown that the transsulfuration pathway is affected after 48 h of treatment (6 replicates per group). (c) C4-2 cells were treated with 2.5 µM SISU-102 or 10 µM CH004 for 48 h before the cells were harvested for measuring homocysteine, cystathionine, and pyruvate metabolite levels (n = 4, but 1 replicate was filtered from DMSO and SISU-102 groups due to high variance). Mean ± standard error is displayed in line graphs and dot plots. The p-value CH004 single treatment versus all other groups is shown above CH004 in the pyruvate graph.