Figure 8. Proposed model for hydralazine disruption of EGF receptor pathway in DU145 cell line.

Exposure of PCa cells to hydralazine probably leads to demethylation of a critical gene that codifies a protein X that regulates EGFR phosphorylation. The re-expression of this protein will induce a significant decrease in EGFR phosphorylation and, consequently, in downstream targets, namely, SRC, MEK1/2 and Akt. Reduced expression of SRC may cause a decrease in JNK and C-Jun proto-oncogene leading to decreased motility and invasion capacity of PCa cells. Moreover, a decrease in MAPK pathway induced by SRC and/or directly via EFGR impairment, could explain the decrease in proliferation and cell cycle arrest observed in this cell line after hydralazine exposure. Finally, a decrease in Akt expression may lead to cell death and decreased tumor angiogenesis. The disruption of these cancer networks through deregulation EGF pathway by hydralazine might be responsible for the attenuation of the malignant phenotype of DU145 cells.